Pimenta Luciana de Araújo, Kato Ellen Emi, Sobral Ana Claudia Martins, Duarte Evandro Luiz, Lamy Maria Teresa Moura, Pasqualoto Kerly Fernanda Mesquita, Sampaio Sandra Coccuzzo
Laboratory of Pathophysiology, Butantan Institute, Sao Paulo 05503-900, Brazil.
Department of Pharmacology, University of Sao Paulo, Sao Paulo 05508-900, Brazil.
Cells. 2025 Jul 26;14(15):1159. doi: 10.3390/cells14151159.
Crotoxin (CTX), the main toxin in venom, is a heterodimeric complex known for its antitumoral, anti-inflammatory, and immunomodulatory properties. In macrophages, CTX stimulates energy metabolism, pro-inflammatory cytokines, superoxide production, and lipoxin A secretion while inhibiting macrophage spreading and phagocytosis. These effects are completely blocked by Boc-2, a selective formyl peptide receptors (FPRs) antagonist. Despite the correlation between FPRs and CTX-mediated effects, their involvement in mediating CTX entry into macrophages remains unclear. This study aimed to investigate the involvement of FPRs in CTX entry into monocytes and macrophages. For this, THP-1 cells were silenced for FPRs or treated with Boc-2. Results demonstrated that FPR-related signaling pathways, which influence macrophage functions such as ROS release, phagocytosis, and spreading, were reduced in FPR-silenced cells. However, even in the absence of FPRs, CTX was efficiently internalized by macrophages. These findings suggest that FPRs are essential for the immunomodulatory effects of CTX, but are not involved in CTX internalization.
响尾蛇毒素（CTX）是毒液中的主要毒素，是一种异二聚体复合物，以其抗肿瘤、抗炎和免疫调节特性而闻名。在巨噬细胞中，CTX刺激能量代谢、促炎细胞因子、超氧化物产生和脂氧素A分泌，同时抑制巨噬细胞铺展和吞噬作用。这些作用被Boc-2（一种选择性甲酰肽受体（FPRs）拮抗剂）完全阻断。尽管FPRs与CTX介导的效应之间存在相关性，但其在介导CTX进入巨噬细胞中的作用仍不清楚。本研究旨在调查FPRs在CTX进入单核细胞和巨噬细胞中的作用。为此，对FPRs进行了基因沉默或用Boc-2处理THP-1细胞。结果表明，在FPRs基因沉默的细胞中，影响巨噬细胞功能（如活性氧释放、吞噬作用和铺展）的FPRs相关信号通路减少。然而，即使在没有FPRs的情况下，CTX仍能被巨噬细胞有效内化。这些发现表明，FPRs对CTX的免疫调节作用至关重要，但不参与CTX的内化。
