17 results on '"Sandra Coccuzzo Sampaio"'
Search Results
2. Crotoxin modulates inflammation and macrophages’ functions in a murine sepsis model
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Marisa Langeani Bretones, Sandra Coccuzzo Sampaio, Denise Frediani Barbeiro, Suely K.Kubo Ariga, Francisco Garcia Soriano, and Thais Martins de Lima
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Inflammation ,Male ,Mice, Inbred BALB C ,Interleukin-6 ,Macrophages ,Crotalus ,Hydrogen Peroxide ,Crotoxin ,Toxicology ,Interleukin-10 ,Mice ,Sepsis ,Escherichia coli ,Animals - Abstract
Sepsis is a syndrome of physiological and biochemical abnormalities induced by an infection that represents a major public health concern. It involves the early activation of inflammatory responses. Crotoxin (CTX), the major toxin of the South American rattlesnake Crotalus durissus terrificus venom, presents longstanding anti-inflammatory properties. Since immune system modulation may be a strategic target in sepsis management, and macrophages' functional and secretory activities are related to the disease's progression, we evaluated the effects of CTX on macrophages from septic animals. Balb/c male mice submitted to cecal ligation and puncture (CLP) were treated with CTX (0.9 μg/animal, subcutaneously) 1 h after the procedure and euthanized after 6 h. We used plasma samples to quantify circulating cytokines and eicosanoids. Bone marrow differentiated macrophages (BMDM) were used to evaluate the CTX effect on macrophages' functions. Our data show that CTX administration increased the survival rate of the animals from 40% to 80%. Septic mice presented lower plasma concentrations of IL-6 and TNF-α after CTX treatment, and higher concentrations of LXA
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- 2022
3. Crotoxin, a rattlesnake toxin, down-modulates functions of bone marrow neutrophils and impairs the Syk-GTPase pathway
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Maria Cristina Cirillo, Vanessa Zambelli, Camila L. Neves, Sandra Coccuzzo Sampaio, Flavia Souza Ribeiro Lopes, and Tatiane S. Lima
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0301 basic medicine ,RHOA ,Neutrophils ,Phagocytosis ,Anti-Inflammatory Agents ,Syk ,Bone Marrow Cells ,Biology ,Toxicology ,GTP Phosphohydrolases ,03 medical and health sciences ,Cell Adhesion ,medicine ,Animals ,Opsonin ,Innate immune system ,030102 biochemistry & molecular biology ,Chemotaxis ,Crotalus ,Degranulation ,Crotoxin ,Fibronectins ,Receptors, Complement ,Cell biology ,Mice, Inbred C57BL ,030104 developmental biology ,medicine.anatomical_structure ,Immunology ,biology.protein ,Bone marrow ,Reactive Oxygen Species ,Signal Transduction - Abstract
Neutrophils have a critical role in the innate immune response; these cells represent the primary line of defense against invading pathogens or tissue injury. Crotoxin (CTX), the major toxin of the South American rattlesnake (Crotalus durissus terrificus) venom, presents longstanding anti-inflammatory properties, inhibiting neutrophil migration and phagocytosis by peritoneal neutrophils for 14 days. Herein, to elucidate these sustained inhibitory effects induced by CTX, we performed in vitro and in vivo studies evaluating the functionality of bone marrow neutrophils and possible molecular mechanisms associated with these effects. CTX inhibited the processes of chemotaxis, adhesion to fibronectin, and phagocytosis of opsonized particles; however, it did not affect ROS production or degranulation in bone marrow neutrophils. To understand the molecular mechanisms that orchestrate this effect, we investigated the expression of CR3 on the neutrophil surface and the total expression and activity of signaling proteins from the Syk-GTPase pathway, which is involved in actin polymerization. CTX down-regulated both subunits of CR3, as well as, the activity of Syk, Vav1, Cdc42, Rac1 and RhoA, and the expression of the subunit 1B from Arp2/3. Together, our findings demonstrated that CTX inhibits the functionally of bone marrow neutrophils and that this effect may be associated with an impairment of the Syk-GTPase pathway. This study demonstrates, for the first time, that the sustained down-modulatory effect of CTX on circulating and peritoneal neutrophils is associated with functional modifications of neutrophils still in the bone marrow, and it also contributes to a better understanding of the anti-inflammatory effect of CTX.
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- 2017
4. Hypanus americanus mucus: A new point of view about stingray immunity and toxins
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Guilherme Rabelo Coelho, Juliana Mozer Sciani, Daniel C. Pimenta, Fernanda D'Amélio, Patrick Jack Spencer, José Pedro Prezotto Neto, Fernanda Cortinhas Barbosa, Sandra Coccuzzo Sampaio, Rafael Silva Santos, and Patricia Brigatte
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Immunity ,Stingray ,Zoology ,Biology ,Toxicology ,Mucus - Published
- 2020
5. Crotoxin modulates the phenotypic reprogramming of quiescent macrophages or stimulated by tumor microenvironment
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Eliana Faquim De Lima Mauro, Camila L. Neves, and Sandra Coccuzzo Sampaio
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Tumor microenvironment ,Biology ,Toxicology ,Phenotype ,Reprogramming ,Cell biology - Published
- 2019
6. Crotoxin, the main rattlesnake toxin from South America, inhibits events involved on epithelial-mesenchymal transition in the 3D-heterospheroid model
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Ellen Emi Kato and Sandra Coccuzzo Sampaio Vessoni
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Toxin ,Chemistry ,medicine ,Epithelial–mesenchymal transition ,Toxicology ,medicine.disease_cause ,Cell biology - Published
- 2019
7. Biochemical composition and inflammatory activity of mucus from Hypanus americanus (Dasyatis americana) marine stingray
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Guilherme Rabelo Coelho, Daniel Carvalho Pimenta, Sandra Coccuzzo Sampaio, Juliana Mozer Sciani, and Rafael Silva Santos
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Stingray ,Biochemical composition ,Zoology ,Dasyatis ,Biology ,Toxicology ,biology.organism_classification ,Mucus - Published
- 2019
8. Inhibitory effect of Crotalus durissus terrificus venom on chronic edema induced by injection of bacillus Calmette-Guérin into the footpad of mice
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Nancy Gimenes da Silva, Luis Roberto de Camargo Gonçalves, and Sandra Coccuzzo Sampaio
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Male ,Injections, Subcutaneous ,Lipoxygenase ,Venom ,Pharmacology ,medicine.disease_cause ,Toxicology ,complex mixtures ,Dexamethasone ,Mice ,Edema ,Crotalid Venoms ,medicine ,Animals ,Hydroxyurea ,Receptor ,Inflammation ,biology ,Foot ,Chemistry ,Toxin ,Anti-Inflammatory Agents, Non-Steroidal ,Crotalus ,Zileuton ,Crotoxin ,Mycobacterium bovis ,Hindlimb ,Snake venom ,Chronic Disease ,Immunology ,BCG Vaccine ,biology.protein ,medicine.symptom ,medicine.drug - Abstract
In this study, we evaluated the effect of the Crotalus durissus terrificus (Cdt) venom on the chronic paw edema induced by the injection of bacillus Calmette-Guerin (BCG) into the footpad of mice. The BCG injection evoked chronic edema, which was significantly diminished in animals treated subcutaneously (s.c.) with Cdt venom 1 h before or after the BCG injection. This inhibition persisted throughout the evaluation period (15 days). In mice injected with Cdt venom 6 or 11 days after injection of BCG, we observed a significant reduction in edema only in the period after the venom injection. While studying possible mechanisms involved in this inhibition, we observed that pre-treatment with dexamethasone, zileuton or Boc2 (a selective antagonist of formyl peptide receptors), but not with indomethacin, canceled out the inhibitory effect of Cdt venom on the edema induced by BCG. These results strongly suggest that this rattlesnake venom can stimulate the generation of mediators from the lipoxygenase pathway, which can down-regulate this chronic inflammatory edema. Using fractionated venom, the results indicated that crotoxin was the only component of Cdt venom responsible for this inhibitory effect. These results indicated that crotoxin, the main toxin of the C. durissus terrificus venom, has a significant inhibitory effect on BCG-induced chronic edema, possibly by generating anti-inflammatory mediators from the lipoxygenase pathway.
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- 2013
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9. Crotoxin: Novel activities for a classic β-neurotoxin
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Angelo J. Magro, Sandra Coccuzzo Sampaio, Patricia Brigatte, Stephen Hyslop, Vanessa Zambelli, Yara Cury, Vanessa Pacciari Gutierrez, J. Prado-Franceschi, and Marcos R.M. Fontes
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Myotoxin ,Neurotoxins ,Antineoplastic Agents ,Venom ,Pharmacology ,Biology ,Toxicology ,medicine.disease_cause ,Immunomodulation ,Structure-Activity Relationship ,Anti-Infective Agents ,medicine ,Animals ,Humans ,Structure–activity relationship ,Neurotoxin ,Protein Structure, Quaternary ,Analgesics ,Phospholipase A ,Toxin ,Anti-Inflammatory Agents, Non-Steroidal ,Crotalus ,Neurotoxicity ,Crotoxin ,medicine.disease ,Disease Models, Animal ,Phospholipases A2 ,Snake venom ,Dimerization - Abstract
Crotoxin, the main toxin of South American rattlesnake (Crotalus durissus terrificus) venom, was the first snake venom protein to be purified and crystallized. Crotoxin is a heterodimeric beta-neurotoxin that consists of a weakly toxic basic phospholipase A(2) and a non-enzymatic, non-toxic acidic component (crotapotin). The classic biological activities normally attributed to crotoxin include neurotoxicity, myotoxicity, nephrotoxicity and cardiotoxicity. However, numerous studies in recent years have shown that crotoxin also has immunomodulatory, anti-inflammatory, anti-microbial, anti-tumor and analgesic actions. In this review, we describe the historical background to the discovery of crotoxin and its main toxic activities and then discuss recent structure-function studies and investigations that have led to the identification of novel pharmacological activities for the toxin.
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- 2010
10. Crotoxin is responsible for the long-lasting anti-inflammatory effect of Crotalus durissus terrificus snake venom: involvement of formyl peptide receptors
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Bianca Cestari Zychar, Maisa S. Della-Casa, Maria Cristina Cirillo, Sandra Coccuzzo Sampaio, F. P. B. Nunes, and Luis Roberto de Camargo Gonçalves
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Male ,medicine.drug_class ,Venom ,Inflammation ,Biology ,Pharmacology ,Carrageenan ,Toxicology ,Anti-inflammatory ,Mice ,chemistry.chemical_compound ,Cell Movement ,Edema ,Leukocytes ,medicine ,Animals ,Muscle, Skeletal ,Receptor ,Microcirculation ,Anti-Inflammatory Agents, Non-Steroidal ,Crotalus ,Crotoxin ,Receptors, Formyl Peptide ,Hindlimb ,Disease Models, Animal ,chemistry ,Mechanism of action ,Snake venom ,Immunology ,Endothelium, Vascular ,Peritoneum ,medicine.symptom - Abstract
In the present study, it was investigated which components are responsible for the anti-inflammatory properties of Crotalus durissus terrificus venom (CdtV). The effect of crotoxin, as well as of other CdtV components was evaluated on edema, cell migration and alterations in leukocyte-endothelium interactions induced by carrageenan. Crotoxin (40 microg kg(-1)) was injected at different time periods before or after the injection of carrageenan (15 mg kg(-1)) into the mouse hind paw, peritoneum or scrotum. Results showed that crotoxin, but not other CdtV components, significantly inhibited inflammatory edema and cell migration when administered before or after carrageenan injection in mice. This toxin also prevented the occurrence of alterations in leukocyte-endothelium interactions induced by carrageenan injection, such as the increase in adhered cells. In animals pretreated with Boc2 (a selective antagonist of formyl peptide receptors), crotoxin showed neither inhibitory effects on edema and cell migration, nor prevented alterations in leukocyte-endothelium interactions induced by carrageenan. These findings demonstrate that crotoxin is the component responsible for the long-lasting anti-inflammatory activity of crude C. durissus terrificus venom, and activation of formyl peptide receptors seems to play a major role in this effect.
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- 2010
11. Crotoxin alters lymphocyte distribution in rats: Involvement of adhesion molecules and lipoxygenase-derived mediators
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Diva Denelle Spadacci-Morena, Luiz Roberto Giorgetti de Britto, Yara Cury, Sandra Coccuzzo Sampaio, Lia Siguemi Sudo-Hayashi, Maisa S. Della-Casa, Rui Curi, Luis Roberto de Camargo Gonçalves, Rosemari Otton, Vanessa Zambelli, Adilson S. Alves, Karin Vicente Greco, and Bianca Cestari Zychar
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Male ,Endothelium ,Lymphocyte ,Lipoxygenase ,High endothelial venules ,Spleen ,Pharmacology ,Biology ,Toxicology ,Thoracic Duct ,Cell Adhesion ,medicine ,Animals ,Hydroxyurea ,Lipoxygenase Inhibitors ,Lymphocyte Count ,Lymphocytes ,Rats, Wistar ,Lymphatic Vessels ,Cell adhesion molecule ,Endothelial Cells ,Crotoxin ,Rats ,Phospholipases A2 ,medicine.anatomical_structure ,Lymphatic system ,Lymph circulation ,Immunology ,Eicosanoids ,Lymph ,Lymph Nodes ,Cell Adhesion Molecules - Abstract
Crotoxin is the main neurotoxic component of Crotalus durissus terrificus snake venom and modulates immune and inflammatory responses, interfering with the activity of leukocytes. In the present work, the effects of crotoxin on the number of blood and lymphatic leukocytes and on lymph nodes and spleen lymphocytes population were investigated. The toxin s.c. administered to male Wistar rats, decreases the number of lymphocytes in blood and lymph circulation and increases the content of B and T-lymphocytes in lymph nodes. These effects were detected 1-2h after treatment. The crotoxin molecule is composed of two subunits, an acidic non-toxic polypeptide, named crotapotin and a toxic basic phospholipase A(2) (PLA(2)). PLA(2), but not crotapotin, decreased the number of circulating blood and lymph lymphocytes. Crotoxin promotes leukocyte adherence to endothelial cells of blood microcirculation and to lymph node high endothelial venules, which might contribute to the drop in the number of circulating lymphocytes. Crotoxin increases expression of the adhesion molecule LFA-1 in lymphocytes. The changes in the expression of the adhesion molecule might contribute, at least in part, for the increased leukocyte adhesion to endothelium. Zileuton, a 5-lipoxygenase inhibitor, blocked the decrease in the number of circulating leukocytes induced by crotoxin and also abolished the changes observed in leukocyte-endothelial interactions, suggesting the involvement of lipoxygenase-derived mediators in the effects of the toxin.
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- 2008
12. Long-lasting anti-inflammatory properties of Crotalus durissus terrificus snake venom in mice
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Sandra Coccuzzo Sampaio, Fernanda P.B. Nunes, Maria Cristina Cirillo Sousa-e-Silva, and Marcelo L. Santoro
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Neutrophils ,Ratón ,medicine.drug_class ,Anti-Inflammatory Agents ,Inflammation ,Venom ,Biology ,Pharmacology ,Carrageenan ,Toxicology ,Anti-inflammatory ,Mice ,Peritoneal cavity ,chemistry.chemical_compound ,Cell Movement ,Edema ,Crotalid Venoms ,medicine ,Animals ,Analysis of Variance ,Crotalus ,medicine.anatomical_structure ,chemistry ,Snake venom ,Immunology ,medicine.symptom - Abstract
In the present study, we investigated the effects of Crotalus durissus terrificus venom ( Cdt V) on vascular and cellular events of inflammation induced by carrageenan (cg) in mice. To evaluate edema, Cdt V (75 μg kg −1 ) was administered subcutaneously before (1 h, 7 or 14 days) or after (1, 4 or 48 h) subplantar injection of cg (15 mg kg −1 ) into the mouse right hind paw; to analyze leukocyte influx, cg (200 μL) was injected i.p. in mice. The inhibitory action of Cdt V on edema, either before or after cg injection, was prolonged, lasting even 72 h after administration. Besides, Cdt V significantly inhibited migration of polymorphonuclear cells to peritoneal cavity when administered before or after cg. Such inhibitory effects of Cdt V on edema and cell migration were also compared with well-known anti-inflammatory drugs. The results demonstrated that Cdt V, when injected either 7 or 14 days or 1 h before cg, induced a more effective and long-lasting anti-inflammatory effect than that observed with classical anti-inflammatory drugs. The association of Cdt V with different drugs did not potentialize their actions on cell migration. These results demonstrate that Cdt V exhibits long-lasting anti-inflammatory effects.
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- 2007
13. Lipoxygenase-derived eicosanoids are involved in the inhibitory effect of Crotalus durissus terrificus venom or crotoxin on rat macrophage phagocytosis
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Patricia Brigatte, Tatiana Carolina Alba-Loureiro, Sandra Coccuzzo Sampaio, Rui Curi, E. C. dos Santos, Richardt G. Landgraf, and Yara Cury
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Male ,Leukotriene B4 ,Phagocytosis ,Lipoxygenase ,Venom ,Pharmacology ,Toxicology ,complex mixtures ,chemistry.chemical_compound ,Phospholipase A2 ,Crotalid Venoms ,Animals ,Macrophage ,Rats, Wistar ,Lipoxin ,Dose-Response Relationship, Drug ,biology ,Crotalus ,Crotoxin ,Rats ,Eicosanoid ,chemistry ,Biochemistry ,Snake venom ,Macrophages, Peritoneal ,biology.protein ,Eicosanoids ,lipids (amino acids, peptides, and proteins) - Abstract
Crotalus durissus terrificus snake venom and its major toxin, crotoxin or type II PLA2 subunit of this toxin, induce an inhibitory effect on spreading and phagocytosis in 2h incubated macrophages. The involvement of arachidonate-derived mediators on the inhibitory action of the venom or toxins on rat peritoneal macrophage phagocytosis was presently investigated. Peritoneal cells harvested from naive rats and incubated with the venom or toxins or harvested from the peritoneal cavity of rats pre-treated with the toxins were used. Zileuton, a 5-lipoxygenase inhibitor but not indomethacin, a cyclooxygenase inhibitor, given in vivo and in vitro abolished the inhibitory effect of venom or toxins on phagocytosis. Resident peritoneal macrophages incubated with the venom or toxins showed increased levels of prostaglandin E2 and lipoxin A4, with no change in leukotriene B4. These results suggest that lipoxygenase-derived eicosanoids are involved in the inhibitory effect of C.d. terrificus venom, crotoxin or PLA2 on macrophage phagocytosis.
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- 2006
14. Peripheral interactions between cannabinoid and opioid systems contribute to the antinociceptive effect of crotalphine
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Sandra Coccuzzo Sampaio, Andrea S. Heimann, C. Remuzgo, Yara Cury, Gisele Picolo, and F.C. Machado
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Nociception ,Opioid ,Crotalphine ,business.industry ,medicine.medical_treatment ,medicine ,Cannabinoid ,Pharmacology ,Toxicology ,business ,medicine.drug ,Peripheral - Published
- 2016
15. Contribution of crotoxin for the inhibitory effect of Crotalus durissus terrificus snake venom on macrophage function
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M. C. C. Sousa-e-Silva, E.C dos-Santos, Sandra Coccuzzo Sampaio, Rui Curi, A.C. Rangel-Santos, Patricia Brigatte, and Yara Cury
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Male ,Erythrocytes ,Injections, Subcutaneous ,Phagocytosis ,Antivenom ,Venom ,(+)-Naloxone ,Pharmacology ,Biology ,Nitric Oxide ,Toxicology ,complex mixtures ,Neutralization Tests ,Candida albicans ,Animals ,Macrophage ,Rats, Wistar ,Receptor ,Cells, Cultured ,Sheep ,Dose-Response Relationship, Drug ,Antivenins ,Naloxone ,Crotalus ,Hydrogen Peroxide ,Crotoxin ,Rats ,Snake venom ,Toxicity ,Immunology ,Macrophages, Peritoneal - Abstract
Previous work of our group demonstrated that Crotalus durissus terrificus venom has a dual effect on macrophage function: it inhibits spreading and phagocytosis and stimulates hydrogen peroxide and nitric oxide production, antimicrobial activity and glucose and glutamine metabolism of these cells. Crotalid venom also induces analgesia and this effect is mediated by opioid receptors. The involvement of opioidergic mechanism and the determination of the active component responsible for the inhibitory effect of crotalid venom on macrophage function were investigated. The venom reduced the spreading and phagocytic activities of peritoneal macrophages. This effect was observed in vitro, 2 h after incubation of resident peritoneal macrophages with the venom, and in vivo, 2 h after subcutaneous injection of the venom. The inhibition of phagocytosis was not modified by naloxone, an antagonist of opioid receptors. Venom neutralization with crotalid antivenom abolished the inhibitory effect of the venom, indicating that venom toxins are involved in this effect. Crotoxin, the main toxin of crotalid venom, s.c. injected to rats or added to the medium of peritoneal cell incubation, inhibited macrophage function in a similar manner to that observed for crude venom. The present results suggest that crotoxin causes a direct inhibition of macrophage spreading and phagocytic activities and may contribute to the inhibitory effect of crotalid venom on macrophage function.
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- 2003
16. 152. Effect of Crotoxin on Secretory Activity of Peritoneal Macrophages Co-cultivated with Tumor Cells. Involvement of Formyl Peptide Receptors
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Edilene S. Costa, Rui Curi, Sandra Coccuzzo Sampaio, Odair Jorge Faiad, and Yara Cury
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Formyl peptide ,Chemistry ,Tumor cells ,Toxicology ,Receptor ,Molecular biology - Published
- 2012
17. Involvement of formyl peptide receptors in the stimulatory effect of crotoxin on macrophages co-cultivated with tumour cells
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Sandra Coccuzzo Sampaio, Patricia Brigatte, Rui Curi, Odair Jorge Faiad, A.K. Ferreira, Yara Cury, Richardt G. Landgraf, and E.S. Costa
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Formyl peptide ,Male ,Walker 256 tumour cells ,Biology ,Toxicology ,Nitric Oxide ,Crotalus durissus terrificus ,Lipoxin and analogues ,Cell Line, Tumor ,Macrophage ,Animals ,Rats, Wistar ,Tumour cells ,Receptor ,Inhibitory effect ,Cell Proliferation ,Cell growth ,Macrophages ,Crotalus ,Hydrogen Peroxide ,Cell–cell interactions ,Crotoxin ,Molecular biology ,Receptors, Formyl Peptide ,Coculture Techniques ,Rats ,Lipoxins ,FISIOLOGIA ,Biochemistry ,Snake venom ,Oxidative metabolism ,Function (biology) ,Snake Venoms - Abstract
Crotoxin (CTX) is the main neurotoxic component of Crotalus durissus terrificus snake venom. It inhibits tumour growth and modulates the function of macrophages, which are essential cells in the tumour microenvironment. The present study investigated the effect of CTX on the secretory activity of monocultured macrophages and macrophages co-cultivated with LLC-WRC 256 cells. The effect of the macrophage secretory activities on tumour cell proliferation was also evaluated. Macrophages pre-treated with CTX (0.3 μg/mL) for 2 h were co-cultivated with LLC-WRC 256 cells, and the secretory activity of the macrophages was determined after 12, 24 and 48 h. The co-cultivation of CTX-treated macrophages with the tumour cells caused a 20% reduction in tumour cell proliferation. The production of both H2O2 and NO was increased by 41% and 29% after 24 or 48 h of co-cultivation, respectively, compared to the values for the co-cultures of macrophages of control. The level of secreted IL-1β increased by 3.7- and 3.2-fold after 12 h and 24 h of co-cultivation, respectively. Moreover, an increased level of LXA4 (25%) was observed after 24 h of co-cultivation, and a 2.3- and 2.1-fold increased level of 15-epi-LXA4 was observed after 24 h and 48 h, respectively. Boc-2, a selective antagonist of formyl peptide receptors, blocked both the stimulatory effect of CTX on the macrophage secretory activity and the inhibitory effect of these cells on tumour cell proliferation. Taken together, these results indicate that CTX enhanced the secretory activity of macrophages, which may contribute to the antitumour activity of these cells, and that activation of formyl peptide receptors appears to play a major role in this effect.
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