Crotoxin Modulates Macrophage Phenotypic Reprogramming
Macrophage plasticity is a fundamental feature of the immune response since it favors the rapid and adequate change of the functional phenotype in response to the pathogen or the microenvironment. Several studies have shown that Crotoxin (CTX), the major toxin of the <i>Crotalus durissus terri...
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MDPI AG
2023-10-01
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| Series: | Toxins |
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| Online Access: | https://www.mdpi.com/2072-6651/15/10/616 |
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| author | Camila Lima Neves Christiano Marcello Vaz Barbosa Priscila Andrade Ranéia-Silva Eliana L. Faquim-Mauro Sandra Coccuzzo Sampaio |
| author_facet | Camila Lima Neves Christiano Marcello Vaz Barbosa Priscila Andrade Ranéia-Silva Eliana L. Faquim-Mauro Sandra Coccuzzo Sampaio |
| author_sort | Camila Lima Neves |
| collection | DOAJ |
| description | Macrophage plasticity is a fundamental feature of the immune response since it favors the rapid and adequate change of the functional phenotype in response to the pathogen or the microenvironment. Several studies have shown that Crotoxin (CTX), the major toxin of the <i>Crotalus durissus terrificus</i> snake venom, has a long-lasting antitumor effect both in experimental models and in clinical trials. In this study, we show the CTX effect on the phenotypic reprogramming of macrophages in the mesenchymal tumor microenvironment or those obtained from the peritoneal cavity of healthy animals. CTX (0.9 or 5 μg/animal subcutaneously) administered concomitantly with intraperitoneal inoculation of tumor cells (1 × 10<sup>7</sup>/0.5 mL, injected intraperitoneally) of Ehrlich Ascitic Tumor (EAT) modulated the macrophages phenotype (M1), accompanied by increased NO<sup>•</sup> production by cells from ascites, and was evaluated after 13 days. On the other hand, in healthy animals, the phenotypic profile of macrophages was modulated in a dose-dependent way at 0.9 μg/animal: M1 and at 5.0 μg/animal: M2; this was accompanied by increased NO<sup>•</sup> production by peritoneal macrophages only for the dose of 0.9 μg/animal of CTX. This study shows that a single administration of CTX interferes with the phenotypic reprogramming of macrophages, as well as with the secretory state of cells from ascites, influencing events involved with mesenchymal tumor progression. These findings may favor the selection of new therapeutic targets to correct compromised immunity in different systems. |
| first_indexed | 2024-03-10T20:50:38Z |
| format | Article |
| id | doaj.art-95a0ccda980947f189650d93dd7582be |
| institution | Directory Open Access Journal |
| issn | 2072-6651 |
| language | English |
| last_indexed | 2024-03-10T20:50:38Z |
| publishDate | 2023-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Toxins |
| spelling | doaj.art-95a0ccda980947f189650d93dd7582be2023-11-19T18:22:48ZengMDPI AGToxins2072-66512023-10-01151061610.3390/toxins15100616Crotoxin Modulates Macrophage Phenotypic ReprogrammingCamila Lima Neves0Christiano Marcello Vaz Barbosa1Priscila Andrade Ranéia-Silva2Eliana L. Faquim-Mauro3Sandra Coccuzzo Sampaio4Laboratory of Pathophysiology, Butantan Institute, São Paulo 05503-900, BrazilDepartment of Biochemistry, Federal University of São Paulo, São Paulo 04044-020, BrazilDepartment of Clinical Medicine, University of Ribeirão Preto, Campus Guarujá, São Paulo 11440-003, BrazilLaboratory of Immunopathology, Butantan Institute, São Paulo 05503-900, BrazilLaboratory of Pathophysiology, Butantan Institute, São Paulo 05503-900, BrazilMacrophage plasticity is a fundamental feature of the immune response since it favors the rapid and adequate change of the functional phenotype in response to the pathogen or the microenvironment. Several studies have shown that Crotoxin (CTX), the major toxin of the <i>Crotalus durissus terrificus</i> snake venom, has a long-lasting antitumor effect both in experimental models and in clinical trials. In this study, we show the CTX effect on the phenotypic reprogramming of macrophages in the mesenchymal tumor microenvironment or those obtained from the peritoneal cavity of healthy animals. CTX (0.9 or 5 μg/animal subcutaneously) administered concomitantly with intraperitoneal inoculation of tumor cells (1 × 10<sup>7</sup>/0.5 mL, injected intraperitoneally) of Ehrlich Ascitic Tumor (EAT) modulated the macrophages phenotype (M1), accompanied by increased NO<sup>•</sup> production by cells from ascites, and was evaluated after 13 days. On the other hand, in healthy animals, the phenotypic profile of macrophages was modulated in a dose-dependent way at 0.9 μg/animal: M1 and at 5.0 μg/animal: M2; this was accompanied by increased NO<sup>•</sup> production by peritoneal macrophages only for the dose of 0.9 μg/animal of CTX. This study shows that a single administration of CTX interferes with the phenotypic reprogramming of macrophages, as well as with the secretory state of cells from ascites, influencing events involved with mesenchymal tumor progression. These findings may favor the selection of new therapeutic targets to correct compromised immunity in different systems.https://www.mdpi.com/2072-6651/15/10/616rattlesnakemacrophage plasticitycytokinestumor microenvironmentimmunomodulatory effect |
| spellingShingle | Camila Lima Neves Christiano Marcello Vaz Barbosa Priscila Andrade Ranéia-Silva Eliana L. Faquim-Mauro Sandra Coccuzzo Sampaio Crotoxin Modulates Macrophage Phenotypic Reprogramming Toxins rattlesnake macrophage plasticity cytokines tumor microenvironment immunomodulatory effect |
| title | Crotoxin Modulates Macrophage Phenotypic Reprogramming |
| title_full | Crotoxin Modulates Macrophage Phenotypic Reprogramming |
| title_fullStr | Crotoxin Modulates Macrophage Phenotypic Reprogramming |
| title_full_unstemmed | Crotoxin Modulates Macrophage Phenotypic Reprogramming |
| title_short | Crotoxin Modulates Macrophage Phenotypic Reprogramming |
| title_sort | crotoxin modulates macrophage phenotypic reprogramming |
| topic | rattlesnake macrophage plasticity cytokines tumor microenvironment immunomodulatory effect |
| url | https://www.mdpi.com/2072-6651/15/10/616 |
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