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The prenatal diet can program an individual's cardiovascular system towards later higher resting blood pressure and kidney dysfunction, but the extent to which these programmed responses are directly determined by the timing of maternal nutritional manipulation is unknown. In the present study we examined whether maternal nutrient restriction targeted over the period of maximal placental growth, i.e. days 28???80 of gestation, resulted in altered blood pressure or kidney development in the juvenile offspring. This was undertaken in 6-month-old sheep born to mothers fed control (100???150 % of the recommended metabolisable energy (ME) intake for that stage of gestation) or nutrient-restricted (NR; 50 % ME; n 6) diets between days 28 and 80 of gestation. Controls were additionally grouped according to normal (>3, n 7) or low body condition score (LBCS; <2, n 6), thereby enabling us to examine the effect of maternal body composition on later cardiovascular function. From day 80 to term (approximately 147 d) all sheep were fed to 100 % ME. Offspring were weaned at 12 weeks and pasture-reared until 6 months of age when cardiovascular function was determined. Both LBCS and NR sheep tended to have lower resting systolic (control, 85 (SE 2); LBCS, 77 (SE 3); NR, 77 (SE 3) mmHg) and diastolic blood pressure relative to controls. Total nephron count was markedly lower in both LBCS and NR relative to controls (LBCS, 59 (SE 6); NR, 56 (SE 12) %). Our data suggest that maternal body composition around conception is as important as the level of nutrient intake during early pregnancy in programming later cardiovascular health. [ABSTRACT FROM PUBLISHER]

The ability of nedocromil sodium, a new anti-inflammatory agent for the treatment of asthma, to inhibit activation of human eosinophils and neutrophils in vitro, has been studied using an adherence reaction (the "rosette" technique) as well as a cytotoxicity assay. We have also investigated the capacity of nedocromil sodium to inhibit IgE-dependent histamine release from human lung mast cells. The drug was a potent inhibitor (IC50 approx 5 × 10-9M) of fMLP-induced enhancement of eosinophil and neutrophil complement (C3b) and IgG (Fc) rosettes. There was also a comparable inhibition of enhancement, by fMLP, of eosinophil and neutrophil cytotoxicity (for complement-coated schistosomula of Schistosoma mansoni). Although nedocromil sodium also inhibited histamine release from human lung mast cells in a dose-dependent fashion its activity was relatively weak (IC30 5 × 10-6M) compared to its effect on granulocytes. These experiments support the view that the principal mode of action of nedocromil sodium is its capacity to inhibit the activation of inflammatory cells. [ABSTRACT FROM AUTHOR]

Background & Aims: Intrahepatic cholestasis of pregnancy (ICP) is associated with an increased risk of stillbirth. This study aimed to assess the relationship between bile acid concentrations and fetal cardiac dysfunction in patients with ICP who were or were not treated with ursodeoxycholic acid (UDCA)., Methods: Bile acid profiles and NT-proBNP, a marker of ventricular dysfunction, were assayed in umbilical venous serum from 15 controls and 76 ICP cases (36 untreated, 40 UDCA-treated). Fetal electrocardiogram traces were obtained from 43 controls and 48 ICP cases (26 untreated, 22 UDCA-treated). PR interval length and heart rate variability (HRV) parameters were measured in 2 behavioral states (quiet and active sleep)., Results: In untreated ICP, fetal total serum bile acid (TSBA) concentrations (r = 0.49, p = 0.019), hydrophobicity index (r = 0.20, p = 0.039), glycocholate concentrations (r = 0.56, p = 0.007) and taurocholate concentrations (r = 0.44, p = 0.039) positively correlated with fetal NT-proBNP. Maternal TSBA (r = 0.40, p = 0.026) and alanine aminotransferase (r = 0.40, p = 0.046) also positively correlated with fetal NT-proBNP. There were no significant correlations between maternal or fetal serum bile acid concentrations and fetal HRV parameters or NT-proBNP concentrations in the UDCA-treated cohort. Fetal PR interval length positively correlated with maternal TSBA in untreated (r = 0.46, p = 0.027) and UDCA-treated ICP (r = 0.54, p = 0.026). Measures of HRV in active sleep and quiet sleep were significantly higher in untreated ICP cases than controls. HRV values in UDCA-treated cases did not differ from controls., Conclusions: Elevated fetal and maternal serum bile acid concentrations in untreated ICP are associated with an abnormal fetal cardiac phenotype characterized by increased NT-proBNP concentration, PR interval length and HRV. UDCA treatment partially attenuates this phenotype., Lay Summary: The risk of stillbirth in intrahepatic cholestasis of pregnancy (ICP) is linked to the level of bile acids in the mother which are thought to disrupt the baby's heart rhythm. We found that babies of women with untreated ICP have abnormally functioning hearts compared to those without ICP, and the degree of abnormality is closely linked to the level of harmful bile acids in the mother and baby's blood. Babies of women with ICP who received treatment with the drug UDCA do not have the same level of abnormality in their hearts, suggesting that UDCA could be a beneficial treatment in some ICP cases, although further clinical trials are needed to confirm this., Competing Interests: Conflict of interest BHG has previously served as a director for Monica Healthcare Limited and has no commercial or financial connections in the company. CW and HUM are consultants with Mirum Pharmaceuticals and CW is a consultant for GlaxoSmithKline. The remaining authors have no conflicts of interest to disclose. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2021 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Objectives: Postpartum stratification of cardiovascular risk for women with pregnancies complicated by pre-eclampsia is challenging. Our aim was to identify potential clinical and biomarker predictors of future cardiovascular risk at six weeks postpartum in women with hypertensive pregnancies., Study Design: Prospective longitudinal cohort., Main Outcome Measures: Ten year-Framingham cardiovascular risk scores were calculated for 477 women (94 with gestational hypertension, 288 with pre-eclampsia, 30 with superimposed pre-eclampsia, 51 with chronic hypertension, 14 women with uncomplicated pregnancies). B-type natriuretic peptide (BNP), neutrophil gelatinase-associated lipocalin (NGAL) and placental growth factor (PlGF) were quantified at six weeks postpartum., Results: Framingham cardiovascular risk scores were not higher in women with pregnancies complicated by pre-eclampsia than healthy controls, nor were scores higher in women with pre-existing chronic hypertension complicated with superimposed pre-eclampsia compared with those without superimposed pre-eclampsia. Women with gestational hypertension had higher risk scores than women with pre-eclampsia and healthy controls. Established risk factors of cardiovascular disease including diastolic blood pressure and previously diagnosed chronic hypertension were associated with higher scores, and African ethnicity, parity and estimated glomerular filtration rate also were independently associated with higher Framingham risk scores at six weeks postpartum. PlGF, BNP and NGAL concentrations were not associated with Framingham cardiovascular risk scores after adjustment for independent variables., Conclusions: A history of pre-eclampsia or superimposed pre-eclampsia in most recent pregnancy was not associated with elevated Framingham risk score at six weeks postpartum. Established clinical predictors may enable risk stratification at six weeks postpartum, which are not enhanced by the biomarkers included in this study., (Copyright © 2018 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.)

Caveolae regulate many cardiovascular functions and thus could be of interest in relation to pre-eclampsia, a pregnancy specific disorder characterised by hypertension and proteinuria. We examined placental mRNA and protein expression/localisation of the caveolae components Caveolin 1-3, Cavin 1-4 as well as eNOS/iNOS in normotensive control (n = 24) and pre-eclamptic pregnancies (n = 19). Placental mRNA expression of caveolin-1, cavin 1-3, was lower and eNOS expression was increased in pre-eclampsia (P < 0.05 for all). Additionally Caveolin-1 protein expression was also reduced in pre-eclampsia (P = 0.007); this could be an adaptive response in pre-eclampsia, possibly to attenuate the oxidative stress/inflammation., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Hypoxia-inducible factors (HIFs), adenosine and tissue renin-angiotensin-system (RAS) promote angiogenesis and vascularisation. We investigated the temporal expression placental adenosine A2AR receptor and HIF-1α in early pregnancy and at delivery in normotensive (NT) and pre-eclamptic (PE) women. Results were compared to our previously reported angiotensin receptor data. Expression of A2AR and HIF-1α was highest at ≤10 weeks, positively correlated through pregnancy and was higher in PE than NT at delivery. The A2AR associated with the AT4R only in early pregnancy. We suggest adenosine and RAS may interact to promote placentation with a potential adaptation to poor placental perfusion in PE., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Potassium channel α-subunits encoded by KCNQ1-5 genes form voltage-dependent channels (KV7), modulated by KCNE1-5 encoded accessory proteins. The aim was to determine KCNQ and KCNE mRNA expression and assess protein expression/localisation of the KCNQ3 and KCNE5 isoforms in first trimester placental tissue. Placentae were obtained from women undergoing elective surgical termination of pregnancy (TOP) at ≤ 10 weeks' (early TOP) and >10 weeks' (mid TOP) gestations. KCNQ1-5 expression was unchanged during the first trimester. KCNE5 expression increased in mid TOP vs. early TOP samples (P = 0.022). This novel study reports mRNA and protein expression of KV7 channels in first trimester placentae., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Pre-eclampsia is associated with lower serum selenium concentrations and glutathione peroxidase expression/activity; total thyroid hormones are also lower., Objectives, Study Design and Main Outcome Measures: We hypothesised that the placental selenoprotein deiodinase (D3) will be protected in pre-eclampsia due to the hierarchy of selenoprotein biosynthesis in selenium deficiency. Venous blood and tissue from three standardised placental sites were obtained at delivery from 27 normotensive and 23 pre-eclamptic women. mRNA expression and enzyme activity were assessed for both deiodinases (D2 and D3); protein expression/localisation was also measured for D3. FT4, FT3 and TSH concentrations were measured in maternal and umbilical cord blood., Results: No significant differences in D3 mRNA or protein expression between normotensive and pre-eclamptic pregnancies. There was a significant effect of sampling site on placental D3 activity only in pre-eclamptic women (P = 0.034; highest activity nearest the cord). A strong correlation between D3 mRNA expression and enzyme activity existed only in the pre-eclamptic group; further strengthened when controlling for maternal selenium (P < 0.002). No significant differences were observed between groups for any of the maternal thyroid hormones; umbilical TSH concentrations were significantly higher in the pre-eclamptic samples (P < 0.001)., Conclusions: D3 mRNA and protein expression appear to be independent of selenium status. Nevertheless, the positive correlation between D3 mRNA expression and activity evident only in pre-eclampsia, suggests that in normotensive controls, where selenium is higher, translation is not affected, but in pre-eclampsia, where selenium is low, enzyme regulation may be altered. The raised umbilical TSH concentrations in pre-eclampsia may be an adaptive fetal response to maximise iodide uptake., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Introduction: We have previously shown the activation of placental RAS in high altitude normotensive (NT) pregnancies [1], presumably related to hypoxia during placental development. PE incidence is increased at high altitude; hypoxia-reoxygenation injury contributes to the elevated oxidative stress seen in this condition. Binding of Angiotensin II to its type I receptor (AT1R) increases generation of reactive oxygen species and we have shown an increase in AT1R in PE [2]. Therefore we investigated whether the RAS is further augmented in PE at high altitudes., Methods: Biopsies were collected, with informed, written consent, from NT and PE women (ISSHP guidelines) at sea-level (UK) and high altitude, 3100m (Leadville, Colorado) immediately after vaginal delivery or elective non-laboured Caesarean section. mRNA expression of the RAS components (angiotensinogen (AGT), prorenin, prorenin receptor, AT1R and angiotensin type 2 receptor) was determined by qRT-PCR and normalised to 3 stably-expressed housekeeping genes using geNorm. Protein expression was semi-quantitatively assessed by immunohistochemistry (H score) and compared between groups (Mann Whitney U test)., Results: mRNA expression of all RAS components was unaffected by altitude in NT, but significantly lower for all in PE (P=0.026-<0.0001). However, in NT, protein expression of all components except AGT was significantly increased at altitude (P=0.037-<0.001). Protein expression of AGT and AT1R was also increased in altitude PE (P<0.004 for both)., Conclusion: We have shown the placental RAS to be activated at altitude, with apparent differences in transcription/translation. Hypoxia-inducible transcription factors such as HIF-1 enhance transcription and translation of many genes encoding "rescue" proteins; this might explain the effects of altitude in NTs. HIF-1 is increased in PE, which might allow increased protein expression at altitude in spite of lower mRNA., (Copyright © 2013. Published by Elsevier B.V.)

Introduction: Changes in plasma antioxidant trace elements during pregnancy are closely related to mortality and morbidity in the newborn. Deficiencies of specific micronutrient antioxidant activities, associated with copper, selenium, zinc and manganese have previously been associated with pre-eclampsia (PE) at term. The purpose of the present study was to investigate these maternal plasma micronutrient concentrations with associated enzyme activities, specifically the copper-related caeruloplasmin, in a subcohort of the international SCreening fOr Pregnancy Endpoints (SCOPE) study, in early pregnancy, prior to disease onset., Methods: Pre-disease plasma samples (14-16+6 weeks') collected from women who subsequently developed PE (n=245) and age- and BMI-matched uncomplicated normotensive controls (NC; n=471) were used following written informed consent. Micronutrient concentrations were measured by inductively-coupled mass spectrometry and caeruloplasmin activity by colorimetric activity assay., Results: Plasma copper concentrations at 15 weeks' gestation were significantly elevated in women who subsequently developed PE; no differences were seen for all other micronutrients (Table). No differences were seen in caeruloplasmin activity between the two groups. However, a positive association between copper concentration and caeruloplasmin activity was observed (r=0.305; R2=0.093; P<0.0001)., Conclusion: Copper has a dual function in pregnancy, while it may be beneficial as a cofactor for numerous antioxidant enzymes, it also a redox-active transition metal, which catalyses the formation of free radicals and increased levels may contribute to oxidative stress status in PE. These data indicate that although women with PE show significantly higher copper, the caeruloplasmin activity is not significantly higher. It seems that during PE, the activity does not increase proportionally with the levels of copper and may indicate a dysfunction of the antioxidant enzyme. Work is underway to characterise copper-dependent antioxidant superoxide dismutase activity and markers of oxidative stress in these women., Funding: British Heart Foundation (Charity No. 225971)., (Copyright © 2013. Published by Elsevier B.V.)

Introduction: Renal ETK/BMX activity is reduced in preeclampsia. Systemic RAS has been studied in preeclampsia; the renal RAS has not. None of the proteins in either pathway have previously been located in renal tissue from human pregnancy., Objectives: To determine renal expression and distribution of proteins involved in the ETK/BMX and RAS pathways in normal and preeclamptic pregnancy., Methods: Limited residual tissue was available from renal biopsies in eight preeclamptic and seven healthy pregnant women. Immunohistochemistry was performed for AT1R, AT2R, angiotensinogen (AGT), prorenin, unphosphorylated ETK/BMX (uBMX) and phosphorylated ETK/BMX (pBMX). Immunohistochemical scoring was performed semiquantatively by a nephropathologist blinded to the original diagnosis. Results All proteins were renally expressed, AT1R equally in glomeruli and tubules, AT2R and prorenin more strongly in the tubules. If at all, uBMX was weakly expressed in glomeruli, and no glomerular pBMX expression was detected. Both uBMX and pBMX were strongly expressed in distal tubules. The material was too limited to detect differences between groups., Conclusion: The presence of prorenin, and both angiotensin receptors in the proximal tubule may indicate activation of the intra-renal RAS. Angiotensin II promotes sodium retention at the proximal tubule independently of aldosterone. Activated ETK/BMX in injured tubular epithelial cells is associated with cell repair and regeneration, proliferation and motility., (Copyright © 2013. Published by Elsevier B.V.)

There is an inverse correlation between human birthweight and umbilical venous angiotensin II (AngII) concentrations. Oxidative stress and increased pro-renin receptor (PRR) both enhance the cleavage of angiotensin I from angiotensinogen (AGT). Pre-eclampsia, a hypertensive disorder of pregnancy, manifests as high blood pressure and proteinuria, and is a state of increased oxidative stress., Hypothesis: Pre-eclampsia will be associated with increased placental expression of components of the renin-angiotensin system, which could result in reduced infant birthweight. Biopsies were taken 1 cm from the placental edge from 27 normotensive controls and 23 pre-eclamptic White European women. Immunohistochemistry was performed for AGT, PRR, glutathione peroxidase 3 (GPx3) and the AT1R and AT2R AngII receptors. Protein expression was semi-quantitatively assessed (H-score)., Results: AT1R expression was significantly increased in pre-eclamptic placentae, and negatively correlated with birthweight (r = -0.529, P = 0.009). AT1R expression was also negatively correlated with GPx3 expression overall (r = -0.647; P = 0.005). AT2R expression positively correlated with AGT (r = 0.615, P = 0.002) in the pre-eclamptic placentae only., Conclusions: The raised AT1R expression in pre-eclampsia, together with inadequate antioxidant protection, possibly through lower GPx activity, might enhance the vasoconstrictor effect of locally-generated AngII, contributing to the restricted fetal growth characteristic of pre-eclampsia. Conversely, the AT2R:AGT association within the pre-eclamptic placenta may provide a compensatory mechanism., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Introduction: Potassium channel α-subunits encoded by KCNQ1-5 genes (Kv7) form voltage-dependent channels that can be modulated by KCNE1-5 encoded accessory proteins. These channels are known to play a role in the reactivity of blood vessels. We have previously shown that both mRNA and protein expression for the novel combination of KCNQ3 and KCNE5 are increased in term and preterm pre-eclampsia (PE) compared to normotensive control placentae [1]. The expression of these isoforms in early placental tissue has not been examined., Objectives: The aims of this study were to determine whether KCNQ3 and KCNE5 mRNA and proteins are expressed in first trimester placental tissue., Methods: Placental samples were obtained from women undergoing elective surgical termination of pregnancy between 6 and 12 weeks' gestation (n=7) following informed written consent. KCNQ3 and KCNE5 mRNA expression was measured by qRT-PCR and normalised to stably expressed GAPDH. Immunohistochemistry was used to assess protein expression and localisation of the isoforms., Results: Both mRNA and protein expression of KCNQ3 and KCNE5 were detected in placental tissue at all gestations. KCNE5 mRNA expression remained constant between 6 and 10 weeks with a subsequent rise at 11 and 12 weeks. KCNQ3 mRNA expression was initially lower than KCNE5 but markedly increased at 7 weeks remaining high until 10 weeks and falling below KCNE5 levels by 12 weeks. Protein expression for both KCNQ3 and KCNE5 was localised mainly to the syncytiotrophoblast but was also evident in the mesenchyme; overall KCNQ3 intensity significantly increased with gestational age (p=0.044)., Conclusion: KCNQ3 and KCNE5 channel isoforms are highly expressed in first trimester placenta. The temporal changes in mRNA expression mirror changes in the placental tissue oxygen tension which increases between 8 and 10 weeks. This would precede the dislocation of the spiral artery plugs enabling maternal blood to flow freely and continuously into the intervillous spaces. We speculate that the increase in mesenchymal protein expression may be related to angiogenesis during this critical window of feto-placental vascular development. Future work will characterise the complete KCNQ/KCNE isoforms in first trimester placental tissue and assess potential functional roles of these channels both in early placentation and in relation to PE., Funding: Tommy's Charity (Registered charity 1060508)., (Copyright © 2012. Published by Elsevier B.V.)

Preeclampsia is a pregnancy-specific condition affecting 2-7% of women and a leading cause of perinatal and maternal morbidity and mortality; it may also predispose the mother and fetus to increased risks of adult cardiovascular disease. The selenoprotein glutathione peroxidases (GPxs) have critical roles in regulating antioxidant status., Objectives, Study Design and Main Outcome Measures: Immunohistochemical measurements of GPx1, GPx3 and GPx4 protein expression were performed on samples taken from three standardised sampling sites between the cord insertion and the periphery of the placenta from 12 normotensive, and 12 preeclamptic women to establish if their expression differed between sampling sites. Total GPx activities were also examined from the three sampling sites of these placentae., Results: There were highly significant reductions in overall immunohistochemical staining of all 3 GPxs in the preeclampsia compared to normotensive placentae (GPx1: P=0.016; GPx3: P=0.003; GPx4: P<0.001). Furthermore, graded differences in expression between the standardised placental sampling sites were also found for GPx3 (higher in the inner region, P=0.05) and GPx4 (higher in the periphery, P=0.02) but not GPx1. Placental GPx enzyme activity was also significantly reduced in tissue from preeclamptic women as compared to normotensive women (P=0.007; the difference was more pronounced nearest the cord insertion)., Conclusions: We have shown highly significant reductions in expression of all three major classes of GPx in placentae from women with preeclampsia, and distribution gradients in activity, which may relate to the differential oxygenation of regions of the placenta., ((c) 2010 Elsevier Ltd. All rights reserved.)

1. We studied neutrophil-activating peptide-1/interleukin-8 in inflammatory bowel disease. 2. Mucosal levels of neutrophil-activating peptide-1/interleukin-8 were significantly higher in patients with active ulcerative colitis [median 74.5 (range 17.7-450.8) pg/mg] than in patients with active Crohn's disease [10.4 (4-46.9) pg/mg; P less than 0.002] or in normal control subjects [10.4 (4-16.6) pg/mg; P less than 0.002]. 3. Circulating neutrophil-activating peptide-1/interleukin-8 was generally undetectable but there were higher levels of anti-neutrophil-activating peptide-1/interleukin-8 antibodies in patients with active ulcerative colitis [62.9 (3.4-239) ng/ml] than in patients with active Crohn's disease [5.9 (2.1-18.10) ng/ml; P less than 0.001] or in control subjects [6.1 (3.2-15.8) ng/ml; P less than 0.001]. 4. Neutrophil-activating peptide-1/interleukin-8 may be of specific functional importance in mediating inflammation in ulcerative colitis.

The possible involvement of two arachidonic acid metabolites, prostaglandin F2 alpha (PGF2 alpha) and leukotriene B4 (LTB4), in the stimulatory effect of human chorionic gonadotrophin (hCG) on the volume of interstitial fluid (IF) in the rat testis has been investigated. Administration of hCG caused a time- and dose-dependent increase in the IF levels of PGF2 alpha while LTB4 showed no clear dose-dependence, but did decrease significantly at 2-8 h after injection of 100 IU hCG. Administration of ethane dimethane sulphonate (EDS), which specifically destroys Leydig cells, decreased the volume of IF but the IF levels of LTB4 and PGF2 alpha were unchanged. This indicates that although the absence of Leydig cells results in significant changes in IF volume, LTB4 and PGF2 alpha are probably not involved in these changes. Furthermore, these findings suggest that Leydig cells are not the only contributors to LTB4 and prostaglandins E2 and F2 alpha in testicular IF. In rats injected peripherally with hCG, intratesticular administration of the cycloxygenase inhibitor, indomethacin, decreased PGF2 alpha levels in IF after 2 and 4 h but not at later times. However, no inhibitory effect of indomethacin on the hCG-stimulated increase in IF volume was detected; indeed, at 2 h after injection of indomethacin + hCG there was a significant increase in IF volume in the indomethacin-injected testis. It is concluded that, although prostaglandins and LTB4 are secreted into IF in the rat testis, these arachidonic acid metabolites are apparently not the primary mediators of the increase in IF volume that follows hCG treatment.

Sepharose beads coated with IgG stimulate eosinophils to produce leukotriene C4 (LTC4). This observation has been extended with specific immobilized IgG/antigen immune complexes to elicit mediator generation. An extract of Aspergillus fumigatus was covalently coupled to Sepharose beads and incubated with the IgG fraction of immune serum from patients with allergic bronchopulmonary aspergillosis. These beads elicited generation of 7.72 +/- 1.7 pmol of LTC4 immunoreactive material (n = 5) from 1 X 10(6) normal eosinophils of greater than 86% purity, and significantly less LTC4 (0.73 +/- 0.19 pmol per 10(6) cells; n = 3) was produced by eosinophils after incubation with beads treated with IgG from normal nonimmune serum. The maximum antibody-dependent release achieved represented approximately 20% of that induced by the calcium ionophore (A23187). LTC4 was measured by radioimmunoassay and validated by reverse-phase high-performance liquid chromatography. The amount of LTC4 generated was dependent on the concentration of A. fumigatus-specific IgG, and mediator release was completely abolished by prior adsorption of the IgG fraction onto Sepharose-protein A (Staphylococcus aureus). Grass pollen-specific IgG antibody/antigen complexes, in combination with Sepharose beads, also triggered generation of LTC4 immunoreactive material. There was no evidence to suggest that IgE/A. fumigatus immune complexes triggered LTC4 generation, although IgE myeloma protein, in association with Sepharose beads, was a weak stimulus. The efficacy of the IgG immune complex-dependent stimulation of eosinophils suggests a possible physiologic mechanism whereby these cells could participate in the inflammatory changes associated with allergic bronchopulmonary aspergillosis and similar allergic disorders.