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Complement system component 3 deficiency modulates the phenotypic profile of murine macrophages

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Author(s):
da Silva, Tiago Francisco ; Amamura, Thais Akemi ; Valadao, Iuri Cordeiro ; Carneiro, Milena Carvalho ; Freitas, Vanessa Morais ; Lepique, Ana Paula ; Isaac, Lourdes
Total Authors: 7
Document type: Journal article
Source: Cellular Immunology; v. 405, p. 10-pg., 2024-10-28.
Abstract

The Complement System is composed of more than 40 proteins that act in innate and adaptive immunity. C3 is the most abundant one and C3-deficient patients are more susceptible to recurrent and severe infections. Several studies have demonstrated the importance of C3 in controlling infections. However, its role in leukocyte biology is still poorly understood. This study aimed to evaluate several cellular parameters in macrophages from C3deficient mice and compare them to similar cells from wild-type counterparts. We observed that in the absence of C3, the population of F4/80low macrophages in the peritoneal cavity of thioglycolate-treated mice is diminished, probably due to the lack of chemotactic factors like C3a and low levels of C5a. Using fluorescence microscopy analysis, we observed that macrophages from C3-deficient mice exhibited morphological alterations when compared to similar cells from wild-type mice. We observed a significant increase in the expression of CD11c, which is part of CR4 (CD11c/CD18), in macrophages from C3-deficient compared to cells from wild-type mice. Treatment with 12-o-tetradecanoylphorbol-13-acetate, stimulated ROS production and MAPK activation by macrophages. However, these parameters were lower in macrophages from C3-deficient mice when compared to wild-type counterparts. In addition, the phagocytosis of iC3b-opsonized Zymosan particles was diminished in macrophages from C3-deficient mice. Our results suggest that C3 deficiency in C57Black/6 mice may influence specific morphological and functional parameters of macrophages, cells of fundamental importance for both the innate and acquired immune responses. (AU)

FAPESP's process: 19/01435-7 - Evaluation of leptospira phagocytosis by peritoneal macrophages from C3 deficient mice
Grantee:Tiago Francisco da Silva
Support Opportunities: Scholarships in Brazil - Master
FAPESP's process: 17/12924-3 - Etiopathogenesis of Leptospirosis: contribution of the complement system for the control of infection in vivo and in vitro and inflammatory response: identification of gene polymorphisms of the complement system in Leptospirosis patients
Grantee:Lourdes Isaac
Support Opportunities: Research Projects - Thematic Grants