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SARS-CoV-2 is a positive-sense RNA virus and it is the causative agent of the global COVID-19 outbreak. COVID-19 is similar to the previous outbreaks for instance SARS in 2002-2003 and MERS in 2012. As the peptides have many advantages, peptide-based therapeutics might be one of the possible ways in the development of COVID-19 specific drugs. SARS-CoV-2 enters into a human via its S protein by attaching with human hACE2 present on the cell membrane in the lungs and intestines of humans. hACE2 cleaves S protein into the S1 subunit for viral attachment and the S2 subunit for fusion with the host cell membrane. The fusion mechanism forms a six-helical bundle (6-HB) structure which finally fuses the viral envelope with the host cell membrane. hACE2 based peptides such as SBP1 and Spikeplug have shown their potential as antiviral agents. S protein-hACE2 interaction and the SARS-CoV-2 fusion machinery play a crucial part in human viral infection. It is evident that if these interactions could be blocked successfully and efficiently, it could be the way to find the drug for COVID-19. Several peptide-based inhibitors are potent inhibitors of S protein-hACE2 interaction. Similarly, the antiviral activity of the antimicrobial peptide, lactoferrin makes it an important candidate for the COVID-19 drug development process. A candidate drug, RhACE2-APN01 based on recombinant hACE2 peptide has already entered phase II clinical trials. This review sheds light on different aspects of the feasibility of using peptide-based therapeutics as the promising therapeutic route for COVID-19.

The heat treatments applied during the manufacture of infant milk formulas (IMFs) may alter the protein structures and so their behaviour during digestion. The aim of this PhD project was to study the relationship between protein structure within model IMFs and their behaviour during in vitro digestion.Three model IMFs were formulated, differing only in their whey protein (WP) profile to be as close as possible to the protein profile of human milk. The IMFs, with different dry matter contents and therefore protein concentration (1.3% or 5.5%), were heat-treated between 67.5°C and 80°C. The kinetics of heat-induced WP denaturation were studied, then the protein structures generated were characterised for an identical extent of WP denaturation (65%). The kinetics of protein hydrolysis were evaluated using static then dynamic in vitro digestion methods at the infant stage.The results showed that the denaturation kinetics of WPs were slowed down for IMF close to human milk due to the absence of β-LG, regardless of the dry matter content. For an identical extent of WP denaturation, the heat-induced protein structures varied according to the protein profile, the dry matter of IMFs, and the heating conditions, which ultimately impacted the protein behaviour during in vitro digestion.The protein structure could therefore be a lever for the IMF optimisation. These results must be complemented by the evaluation of the physiological impact of these different structures.; Les traitements thermiques appliqués pendant la fabrication des préparations pour nourrissons (PPNs) peuvent altérer les structures des protéines et donc leur comportement au cours de la digestion. L'objectif de ce projet de thèse était d'étudier la relation entre la structure des protéines au sein de PPNs modèles et leur comportement au cours de leur digestion in vitro.Trois PPNs modèles ont été développées, se différenciant par leur profil en protéines du lactosérum (PS) afin de se rapprocher du profil protéique du lait maternel. Les PPNs, avec différentes teneurs en matière sèche et donc concentration protéique (1.3% ou 5.5%), ont été traitées thermiquement entre 67.5°C et 80°C. La cinétique de dénaturation thermique des PS a été étudiée puis les structures protéiques générées ont été caractérisées pour un même taux de dénaturation des PS (65%). La cinétique de digestion protéique a été évaluée en digestion in vitro statique puis dynamique, simulant les conditions physiologiques du nourrisson.Les résultats ont montré que la cinétique de dénaturation des PS était ralentie pour la PPN proche du lait maternel de par l’absence de β-LG, et ce indépendamment de la teneur en matière sèche. Pour un même taux de dénaturation des PS, la structure protéique des PPNs variait selon la composition protéique des PPNs, leur teneur en matière sèche et les conditions thermiques, ce qui, in fine, impactait le devenir des protéines au cours de la digestion in vitro.La structure des protéines pourrait donc être un levier pour l’optimisation des PPNs. Ces résultats doivent être complétés par l’évaluation de l’impact physiologique de ces différentes structures.

The heat treatments applied during the manufacture of infant milk formulas (IMFs) may alter the protein structures and so their behaviour during digestion. The aim of this PhD project was to study the relationship between protein structure within model IMFs and their behaviour during in vitro digestion.Three model IMFs were formulated, differing only in their whey protein (WP) profile to be as close as possible to the protein profile of human milk. The IMFs, with different dry matter contents and therefore protein concentration (1.3% or 5.5%), were heat-treated between 67.5°C and 80°C. The kinetics of heat-induced WP denaturation were studied, then the protein structures generated were characterised for an identical extent of WP denaturation (65%). The kinetics of protein hydrolysis were evaluated using static then dynamic in vitro digestion methods at the infant stage.The results showed that the denaturation kinetics of WPs were slowed down for IMF close to human milk due to the absence of β-LG, regardless of the dry matter content. For an identical extent of WP denaturation, the heat-induced protein structures varied according to the protein profile, the dry matter of IMFs, and the heating conditions, which ultimately impacted the protein behaviour during in vitro digestion.The protein structure could therefore be a lever for the IMF optimisation. These results must be complemented by the evaluation of the physiological impact of these different structures.; Les traitements thermiques appliqués pendant la fabrication des préparations pour nourrissons (PPNs) peuvent altérer les structures des protéines et donc leur comportement au cours de la digestion. L'objectif de ce projet de thèse était d'étudier la relation entre la structure des protéines au sein de PPNs modèles et leur comportement au cours de leur digestion in vitro.Trois PPNs modèles ont été développées, se différenciant par leur profil en protéines du lactosérum (PS) afin de se rapprocher du profil protéique du lait maternel. Les PPNs, avec différentes teneurs en matière sèche et donc concentration protéique (1.3% ou 5.5%), ont été traitées thermiquement entre 67.5°C et 80°C. La cinétique de dénaturation thermique des PS a été étudiée puis les structures protéiques générées ont été caractérisées pour un même taux de dénaturation des PS (65%). La cinétique de digestion protéique a été évaluée en digestion in vitro statique puis dynamique, simulant les conditions physiologiques du nourrisson.Les résultats ont montré que la cinétique de dénaturation des PS était ralentie pour la PPN proche du lait maternel de par l’absence de β-LG, et ce indépendamment de la teneur en matière sèche. Pour un même taux de dénaturation des PS, la structure protéique des PPNs variait selon la composition protéique des PPNs, leur teneur en matière sèche et les conditions thermiques, ce qui, in fine, impactait le devenir des protéines au cours de la digestion in vitro.La structure des protéines pourrait donc être un levier pour l’optimisation des PPNs. Ces résultats doivent être complétés par l’évaluation de l’impact physiologique de ces différentes structures.

Les antibiotiques sont fréquemment utilisés dans l’alimentation de la volaille afin de prévenir certaines maladies, dont l’entérite nécrotique, ce qui occasionne l’émergence de souches bactériennes résistantes aux antibiotiques. Une alternative prometteuse est l’utilisation de peptides antimicrobiens (AMPs) comme suppléments alimentaires, tels les AMPs provenant des produits laitiers. L’objectif du projet était de développer une méthode de production d’extraits peptidiques à partir de coproduits de la transformation alimentaire (babeurre, lactoferrine, isolat de protéines de pois), afin de tester si ces extraits peptidiques possédaient une activité antimicrobienne sur les pathogènes spécifiques aviaires suivants : Salmonella Enteritidis, Salmonella Typhimurium, Escherichia coli et Staphylococcus aureus. Les protéines ont été mises en suspension dans l’eau (5% p/p) et hydrolysées par la pepsine, 6 heures, pH de 2.5. Les peptides furent récupérés par ultrafiltration (< 10 kDa), puis fractionnés selon leur charge nette : totaux, cationiques, anioniques et non liés. L’effet antimicrobien a été évalué surmicroplaques, par la survie bactérienne en présence de concentrations croissantes d’extraits peptidiques. Les extraits cationiques de babeurre ont démontré une efficacité à une concentration inférieure ou égale à 5 mg/mL; perte de 3 log pour Escherichia coli O78 :H80. En comparaison, la lactoferrine cationique a été efficace à une concentration inférieure ou égale à 0.6 mg/mL; perte de 6 log pour E. coli O78 :H80. Les extraits peptidiques du pois ont démontré une efficacité faible. Cette méthode s’avère prometteuse pour le développement d’une alternative ou d’un complément pour la réduction de l’utilisation des antibiotiques dans l’alimentation de la volaille., Antibiotics are frequently used in poultry feed in order to prevent certain diseases, including necrotic enteritis, which causes the emergence of bacterial strains resistant to antibiotics. A promising alternative is the use of antimicrobial peptides (AMPs) as dietary supplements, such as AMPs from dairy products. The objective of this project was to develop a production method for the extraction peptides, from co-produced food processing (buttermilk, lactoferrin, pea protein isolates). These peptides were tested for the detection of antimicrobial activity on the following specific poultry pathogens; Salmonella Enteritidis, Salmonella Typhimurium, Escherichia coli and Staphylococcus aureus. Proteins were suspended in water (5% w/w) and pepsin hydrolyzed by pepsin for 6 hours at pH 2.5. Peptides were recovered by ultrafiltration (< 10 kDa) and fractionated based on the basis of their ionic charges: total, cationic, anionic and unbound peptides, to specifically target the fractions with antimicrobial activities. Bacterial survival was measured in contact with different peptides concentrations. Cationic buttermilk extracts were effective at a concentration less or equal to 5 mg / mL; loss of 3 log for Escherichia coli O78: H80, compared with lactoferrin which was effective at a concentration less than or equal to 0.6 mg / mL; loss of 6 log for E. coli O78: H80. The peptide extracts from pea showed low efficiency. The use of antimicrobial peptides, from buttermilk, lactoferrin and peas, is promising for the development of an alternative or a complement to reduce antimicrobial use.

International audience; Lactoferrin (Lf) is an iron-binding glycoprotein of the transferrin family that is expressed and secreted by glandular cells and found in the secondary granules of neutrophils from which it is released in infected tissues and blood during the inflammatory process. Initially described as an iron-binding molecule with bacteriostatic properties, Lf is now known to be a multifunctional or multi-tasking protein. It is a major component of the innate immune system of mammals. Its protective effects range from direct anti-microbial activities against a large panel of microorganisms including bacteria, viruses, fungi, and parasites, to anti-inflammatory and anti-cancer activities. While iron chelation is central to some of the biological functions of Lf, other activities involve interactions of Lf with molecular and cellular components of both hosts and pathogens. Its powerful antimicrobial activities, immunomodulatory properties and prevention of septic shock, anti-carcinogenic functions and its growing importance in iron delivery and bone growth, combined with the data obtained either by in vivo studies or clinical trials, make this molecule and its derivatives very promising tools for health or nutritional applications. double dagger.

Postharvest diseases are a major concern for several plant products, leading to considerable postharvest losses. Colletotrichum musae is responsible for anthracnose and is also involved in crown rot, the two main postharvest diseases of bananas. The use of natural anti-microbial agents such as the lactoperoxidase system (LPS) represents an interesting alternative to the use of fungicides for the control of postharvest diseases of bananas. This study consisted on optimization of the LPS by adding iodide or substituting the thiocyanate by iodide. Moreover, other substances like lactoferrin, Bioxeda® and Neem oil were analyzed for their antifungal effect. The last two compounds gave an inhibition higher than 90% and 40% respectively. No effect of lactoferrin was observed, L'anthracnose constitue pour plusieurs productions végétales une maladie importante qui engendre des pertes post récoltes considérables. Colletotrichum musae est le responsable de cette maladie chez la banane dessert. L'utilisation d'antimicrobiens naturels comme le système lactoperoxydase (LPS) représente une voie naturelle de lutte intéressante contre l'anthracnose. Dans cette étude, nous avons amélioré le LPS en ajoutant de l'iode dans le système existant ou en substituant le thiocyanate par de l'iode. La substitution du thiocyanate à l'iode a permis d'avoir un effet fongicide du LPS. De plus, d'autres substances comme la lactoferrine, le Bioxeda® et l'huile de Neem ont été étudiées pour leur effet antifongique. Les deux dernières substances ont donné une inhibition supérieure respectivement à 90% et à 40%., tandis qu'il n'y a eu aucun effet de la lactoferrine

Localised seminal vesicle amyloidosis is relatively infrequent and we present 9 additional cases.and methods: Those 9 cases were retrospectively retrieved from 803 radical prostatectomies performed between 1995 and 2000 for prostatic adenocarcinoma. In each case, the type of amyloidosis was characterised by immunohistochemistry. Information regarding a possible concurrent disease or prior hormone therapy has been obtained.The prevalence of amyloidosis of seminal vesicles is lower in our study (1.1%) than in unselected autopsy cases. The prevalence of amyloidosis in patients exposed to prior hormone therapy (LHRH agonist and anti-androgen) was 2% while it reached only 0.9% in those who received no hormone therapy (p0.3). No patient had systemic amyloidosis and all cases were of non A-A type. Lactoferrin, a glycoprotein produced by normal seminal vesicles, was detected in more than a half of them (5/9).No association was found between the occurrence of seminal vesicle amyloidosis and occurrence of a prostatic adenocarcinoma, corcomitant systemic disease or exposure to prior hormone therapy. Seminal vesicle amyloidosis is a localised condition without systemic involvement and amyloid deposition is composed mostly of lactoferrin.

The lacrimal film contains 6 to 10 g/l of proteins, 99% of which locally synthesized by the lacrimal glands. The study of these proteins allows us to explore the lacrimal function and to reveal an inflammatory process.The lacrimal proteinic profile included the determination of total proteins and electrophoresis on agarose gel and, if necessary, specific determinations of albumin, lactoferrin, lysozyme and immunoglobulins using a nephelemetric technique. Normal values were established on a hundred of individual tears.The electrophoretic proteinic profile may present different abnormalities, such as an inflammatory process, a functional alteration of the lacrimal glands or a dysproteinic abnormality of the tears. The specific determination of the principal lacrimal proteins allows us to accurately quantify each of them.The electrophoresis of the tears on an agarose gel reveals the presence of an inflammatory process or the quantitative or qualitative alteration of the lacrimal function. The immuno-nephelemetric determination of the most important proteins which are involved in theses mechanisms gives an accurate quantitative measurement of proteins and allows biological follow-up of the disease.

Lf presented differential effects in the induction of normal human monocyte activation. Lf inhibits the free radical generation by normal human monocytes in response to PMA. This effect on free radical generation is linked to the nature of the divalent cationic metal that substitutes the Apo-Lf. Indeed, the substitution of Fe2+ by another cationic transition metal (Cu2+, Zn2+, Pt2+ or Au2+) modifies the anti-oxidant effect of Lf. Among the different substituted Lf the Lf saturated with Cu2+ is the more potent inhibitor of free radical generation by normal human monocytes. In addition to its anti-oxidant effect, Lf stimulates, in combination with LPS, the production of cytokines (IL-1 beta, TNF-alpha and IL-6) and of prostacyclin (PGI2) by normal human monocytes. This potentiating effect is independent of the cation that substitutes the Lf, since the Apo-Lf is able to induce such a potentiating effect. In addition, whereas Lf does not modulate the phenotype of normal human monocytes stimulated or not with IL-4 it does enhance the IL-4-induced release of the soluble form of CD23 by these cells.

Fifty-nine thyroid tumors were re-examined and studied using immunohistochemistry to detect the presence of ceruloplasmin (CP), lactoferrin (LF), thyroglobulin, thyrocalcitonin, carcinoembryonic antigen and ferritin. In an attempt to study the contribution of the immunodetection of CP and LF in the diagnosis of malignant versus benign tumors, specially in follicular tumors, we compared our results of immunodetection with those of Tuccari and Barresi, and carried out our own studies on the usefulness of these immunolabelling. Concerning CP and LF staining, we have found the following data: 1) little (in contrast to Tuccari and Barresi) or no staining in normal thyroid and benign adenomas; 2) diffuse and intense staining in papillary and follicular carcinomas (as noted by the previous authors); 3) diffuse and weak staining for medullary carcinomas (in contrast to Tuccari and Barresi who found none). Our findings suggest that a diffuse and intense cytoplasmic staining with CP and LF concerning more than one third of all cells is a criterion of malignancy, whereas a weak paranuclear staining of a few cells is more in favor of a benign process.

Fourteen subjects were examined for lactoferrin content in PMNs of venous blood. Eight of the subjects were diagnosed localized juvenile periodontitis (LJP) and four adult periodontitis (AP), all having subgingival occurrence of Actinobacillus actinomycetemcomitans (A.a.). Two subjects had healthy gingival conditions and no detectable A.a. Deficiency or low PMN lactoferrin amounts were found in six of the eight subjects with LJP and in two of the subjects with AP. The reduced lactoferrin content in the PMNs was suggested to be depending on a cytotoxic factor produced by A.a. adding to an intrinsic PMN defect.

Lactoferrin and transferrin exhibit very similar structure and biochemical properties but they behave as two distinct antigens and their affinity for ferric ions is not of the same magnitude. The biological functions of lactoferrin are not all well understood. It has strong bacteriostatic properties, it plays a role as a regulator of human granulopoiesis and it is probably involved in the hyposideremia of acute inflammation. Measurement of lactoferrin was first applied in pancreatic juice or duodenal fluid as a diagnostic tool for pancreatic diseases. More recently plasma lactoferrin has been used as an index of total circulating neutrophil pool in hematological disorders and in uremic patients during hemodialysis. Its clinical usefulness is still discussed for the early diagnostic of infectious diseases.

The tremendous increase in the number of articles from the world scientific literature dealing with the synovial fluid in recent years, reflects the growing interest of research on that subject. The current review summarizes the scientific works published during the period of 1972 to 1975. This review deals with fundamental as well as applied research or clinical reports adding some diagnostic hints in the knowledge of diseases involving joints. The content of the review is divided in two major chapters. 1) The Physico-Chemical Properties of the Synovial Fluid (viscosity, pH,...); 2) The Composition of the Synovial Fluid (proteins, carbohydrates, lipids, prostaglandins, cells, crystals, micro-organisms).

Eight proteins (Immunoglobulin A, G, M, C3 and C4 fractions of complement, alpha 1-glycoprotein, lactoferrin and alpha 1- antitrypsin) were measured by immuno-diffusion or laser nephelometry in 50 milk samples. Thirty nine were heated thrice at 62 degrees C for 20 minutes. Twenty six came from mothers who delivered prematurely (less than 37 weeks) and 13 from mothers who delivered at term. Eleven samples were, used to determine the effect of the heating process. There was no significative difference of the concentrations of the eight proteins between the breast milk obtained at term or prematurely, even when the comparisons were made between colostral milks or transitional milks. The heating process reduced the concentration by 47 % for IgA, more than 88 % for IgG and IgM, 41 to 74 % for the other proteins; only orosomucoid seemed little affected (-16 %). These data suggest that the heating process impairs the immunologic effect of breast milk. This effect must be particularly considered in regard to the absence of any significant difference between the milks obtained at term or prematurely.

For the determination of lactoferrin in human plasma we describe a double-sandwich immunoenzymatic assay in 3 steps using tubes as the solid phase. The analytical performances are acceptable. Within-run and between-run CVs are respectively 4% and 13%, the lower limit of detection is 8 micrograms/l. Sensitivity and specificity are good. The influence on lactoferrin concentration of time elapsing from blood sampling to separation of plasma from cells was studied in order to define the optimal conditions of storage and centrifugation. The range of concentration obtained on 22 healthy adults lies between 59 and 345 micrograms/l.

Plasmatic lactoferrin measure (LF) by immuno-enzymatic technique combined with neutrophil blood count (PN) on 100 subjects (controls and patients) allows us to show a LF increase proportional to circulating blood neutrophils. In neutropenia, plasmatic lactoferrin measure seems able to divide the central causes from the peripheric ones. Regarding the granulocytosis, LF levels are clearly higher in myeloproliferative diseases than in other causes. Lactoferrin could therefore represent an index of total circulating neutrophil pool but also seems to reflect the granulocyte activation.

Mean transferrin and lactoferrin concentrations in whey samples from 376 uninfected quarters of 42 Holstein X Friesian cows on the 30th, 150th and 270th days of lactation were respectively 0.030 and 0.080 mg/ml. The mean transferrin concentration in serum was 4.63 mg/ml. Lactation number and location of quarters did not influence milk lactoferrin and transferrin values. Lactoferrin concentration increased significantly (P less than 0.01) in uninfected quarters from 0.03 to 0.06 and to 0.15 mg/ml on the three successive sampling times. Transferrin whey concentration increased significantly (P less than 0.01) only in late lactation, from 0.025 (30th and 150th days of lactation) to 0.035 mg/ml (270th day of lactation). Lactoferrin concentration increased significantly (P less than 0.01) in quarters infected by major pathogens (41 samples) whereas minor pathogen infections (61 samples) caused no significant increase. The correlation coefficients between milk lactoferrin and transferrin concentrations and somatic cell-count were 0.42 and 0.65 respectively.

Lactotransferrin is involved in the antibacterial defence of the host by virtue of its reversible iron-binding capacity. On the one hand, it participates in different molecular mechanisms displayed by immunocompetent cells which are known to synthesize or recognize the lactotransferrin. For instance, 1) during inflammation, apolactotransferrin released by the neutrophils captures the iron from serotransferrin which is accumulated by the macrophages, by means of their lactotransferrin membrane receptors; 2) lactotransferrin is an important component in the microbicidal activity of neutrophils by regulating the hydroxyl radical production; 3) lactotransferrin acts as a regulator of myelopoiesis by modulating activity of the colony stimulating factors; 4) lactotransferrin could be involved in the control mechanism of lymphoid cell migration. On the other hand, lactotransferrin participates to the non-specific local secretory immunity by being involved in antibacterial mechanisms together with secretory immunoglobulins sIgA and lysozyme. The different aspects of the participation of the lactotransferrin in the cellular and secretory mechanisms of antibacterial defence of the host show that the lactotransferrin plays a predominant role in the local immunity of any mucosa.

The bacteriostatic effect of the association bovine lactoferrin (LF) and bovine IgG (IgG) was studied in vitro and in vivo against two Escherichia coli strains, S17 and EMO1, isolated from the faecal flora of mouse and man, respectively. These two strains were sensitive in vitro to the bacteriostatic effect of LF + IgG. A kinetic study of the in vivo establishment of E. coli S17 was followed in axenic mice associated with that strain. Seven hours after inoculation, no difference was observed in the faecal level of E. coli between control mice and mice fed the same diet supplemented with LF + IgG. An in vivo study was also carried out in human newborns receiving either maternized milk (Nursie) or the same milk supplemented with LF + IgG during the first 48 h of life. One group of babies was inoculated at birth with E. coli EMO1, while another was not. Between the ages of 1 and 5 days, the kinetics of establishment of the E. coli strains spontaneously found in the digestive tract of non-inoculated babies was not significantly different between the group which received milk supplemented with LF + IgG and that which did not. This result was confirmed in infants inoculated with E. coli EMO1. Likewise, the faecal levels of E. coli EMO1 were similar in the supplemented and non-supplemented babies, and, already from day 1, the population level was high and only slight individual variations between babies of the same group were observed. These findings show that the in vitro bacteriostatic effect of LF + IgG on the growth of E. coli strains is not found in vivo.

In 20 patients suffering from chronic renal failure treated by hemodialysis (CRFH) the pure pancreatic juice (PPJ) collected via endoscopic cannulation of the papilla was studied. PPJ was collected during 20 minutes in 1 minute samples. Secretin and pancreozymin (CCK-PZ) were given as boluses respectively at the beginning and at the 10th minute of the test. Volumes, total protein and bicarbonate concentrations, total protein and bicarbonate outputs, Lactoferrin (LF) levels were measured. The results observed in patients were compared to those of ten subjects free of any organic disease. The volume of PPJ was significantly more important in CRFH than in controls. Bicarbonate and protein concentrations were not significantly modified. Protein output was not significantly more important in CRFH at the exception of the 12th sample. Bicarbonate output was not significantly increased at the exception of the 9th and the 11th samples. LF level was more than 0.03% of total proteins in 4 CRFH.

The protein composition of sputum collected by a protected method in 17 children with cystic fibrosis (CF) was analysed. The severity of the disease was assessed using the Shwachman score and the degree of bronchial superinfection was determined by a quantitative cyto-bacteriological study. The main proteins with antibacterial activity (IgA, IgG, IgM, lysozyme and lactoferrin) or reflecting the degree of bronchial inflammation (serumalbumin and alpha 1-antitrypsin) were determined by immunological methods. In the presence of severe superinfection (11 cases out of 17), the concentrations of antibacterial activity proteins are unchanged. On the other hand, the bronchial superinfection is accompanied by a marked local inflammation. In sputa, the increased concentrations of serum-derived proteins are closely correlated to the severity of the disease. This study confirms the importance of bronchial inflammation in CF.

The optimal conditions of the binding of human lactotransferrin to human alveolar macrophages have been determined and the necessity to measure the binding in absence of bovine serum albumin was demonstrated. In these conditions, diferric lactotransferrin and iron-free lactotransferrin are reversibly bound with the following parameters: association constant Ka = 2 and 5 X 10(6) M-1, respectively, and the number of binding sites N = 1.2 and 1 X 10(7), respectively. The binding of the two forms of lactotransferrins was inhibited by various neoglycoproteins, the highest inhibition being obtained with L-fucosyl, then, in the following decreasing order: D-mannosyl greater than N-acetyl-D-glucosaminyl greater than D-galactosyl. In the same conditions, the binding of serotransferrin (Ka = 2 X 10(7) M-1 and 1.6 X 10(7) M-1; N = 5 X 10(4) and 8 X 10(4) for diferric and iron-free protein, respectively) was not inhibited. These results suggest that the recognition of lactotransferrin is mediated by one or several membrane lectins, the fucose being one of the sugar playing an important role in the association. On the contrary, the binding of serotransferrin does not depend on a membrane lectin system.

In a prospective study we have measured the lactoferrin level of duodenal juice under secretin plus caerulein pancreatic stimulation in 78 subjects. Subjects was divided in 4 groups as follows: 27 controls, 11 pancreatic disease without chronic pancreatitis (CP), 17 CP and 23 suspicions of CP. Lactoferrin was assayed by radial immunodiffusion and the level was referred to lipase activity. The test was considered as positive when lactoferrin (microgram/ml) X 100/lipase (U/ml) greater than 0.1. No one control subject had a positive test, 2 pancreatic cancers out of 4, 1 acute pancreatitis out of 7, 12 CP out of 17 had a positive test. The sensitivity (0.71) and the specificity (0.92) of the test do not allow us to propose this test as unequivocal in the diagnosis of CP.

The mechanisms which regulate cellular differentiation from human pluripotent stem cells to the committed granulocytic and monocytic stem cells (CFU-D, CFU-C) are still imperfectly understood. Most studies involve in vitro and animal experimentations and the relevance of the conclusions on human in vivo mechanisms may be questionable. The monocyte-macrophage system figures actually as the major source of humoral regulators of the normal granulocytopoiesis and monocytopoiesis in man. It produces CSF, a family of glycoproteins which stimulate the proliferation and maturation of CFU-c, and PGE which are inhibitory. In addition, CSF may act as a stimulator of the proliferation and myeloid commitment of CFU-S. Several other humoral factors are of less well established importance. Bacterial toxins and antigens are potent stimulators of the production of CSF. Androgens are stimulators of the proliferation of CFU-C. Lactoferrin, a glycoprotein released by granulocytes, may inhibit CSF production by monocytes-macrophages. CIF, a group of lipoproteins, may act as an inactivator of CSF. Granulocyte chalones and interferon may be inhibitors, though poorly specific, of granulopoietic differentiation. Glucocorticoids may exert an inhibitory effect on CFU-C proliferation and CSF release. Precise analysis of the humoral regulation of normal granulocytopoiesis and monocytopoiesis in man seems to be of critical interest in understanding the pathophysiological mechanisms of blood diseases such as leukemias and aplastic anemias.