# Formyl Peptide Receptors 1 and 2: Essential for Immunomodulation of Crotoxin in Human Macrophages, Unrelated to Cellular Entry

## TL;DR

The study shows that formyl peptide receptors are crucial for the immune effects of crotoxin in human macrophages but not for its entry into cells.

## Contribution

The novel finding is that FPRs mediate immunomodulation but not cellular entry of crotoxin in macrophages.

## Key findings

- FPR-related signaling pathways are reduced in FPR-silenced cells, affecting macrophage functions.
- Crotoxin is efficiently internalized by macrophages even in the absence of FPRs.

## Abstract

Crotoxin (CTX), the main toxin in Crotalus durissus terrificus 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 A4 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.