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Volume 14
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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

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

by
Luciana de Araújo Pimenta
1,2,†,
Ellen Emi Kato
1,†,
Ana Claudia Martins Sobral
3,
Evandro Luiz Duarte
4,
Maria Teresa Moura Lamy
4,
Kerly Fernanda Mesquita Pasqualoto
5 and
Sandra Coccuzzo Sampaio
1,2,6,*
1
Laboratory of Pathophysiology, Butantan Institute, Sao Paulo 05503-900, Brazil
2
Department of Pharmacology, University of Sao Paulo, Sao Paulo 05508-900, Brazil
3
Center for Contaminants, Adolfo Lutz Institute, Sao Paulo 01246-000, Brazil
4
Institute of Physics, University of Sao Paulo, Sao Paulo 05508-090, Brazil
5
LIM-14, Faculty of Medicine, University of Sao Paulo, Sao Paulo 05508-000, Brazil
6
Department of Immunology, University of Sao Paulo, Sao Paulo 05508-900, Brazil
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Cells 2025, 14(15), 1159; https://doi.org/10.3390/cells14151159 (registering DOI)
Submission received: 27 June 2025 / Accepted: 23 July 2025 / Published: 26 July 2025
(This article belongs to the Special Issue Study on Immune Activity of Natural Products)
Versions Notes

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.
Keywords: crotoxin; formyl peptides receptors; macrophages; immunomodulation; internalization; in silico study crotoxin; formyl peptides receptors; macrophages; immunomodulation; internalization; in silico study

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MDPI and ACS Style

Pimenta, L.d.A.; Kato, E.E.; Sobral, A.C.M.; Duarte, E.L.; Lamy, M.T.M.; Pasqualoto, K.F.M.; Sampaio, S.C. Formyl Peptide Receptors 1 and 2: Essential for Immunomodulation of Crotoxin in Human Macrophages, Unrelated to Cellular Entry. Cells 2025, 14, 1159. https://doi.org/10.3390/cells14151159

AMA Style

Pimenta LdA, Kato EE, Sobral ACM, Duarte EL, Lamy MTM, Pasqualoto KFM, Sampaio SC. Formyl Peptide Receptors 1 and 2: Essential for Immunomodulation of Crotoxin in Human Macrophages, Unrelated to Cellular Entry. Cells. 2025; 14(15):1159. https://doi.org/10.3390/cells14151159

Chicago/Turabian Style

Pimenta, Luciana de Araújo, Ellen Emi Kato, Ana Claudia Martins Sobral, Evandro Luiz Duarte, Maria Teresa Moura Lamy, Kerly Fernanda Mesquita Pasqualoto, and Sandra Coccuzzo Sampaio. 2025. "Formyl Peptide Receptors 1 and 2: Essential for Immunomodulation of Crotoxin in Human Macrophages, Unrelated to Cellular Entry" Cells 14, no. 15: 1159. https://doi.org/10.3390/cells14151159

APA Style

Pimenta, L. d. A., Kato, E. E., Sobral, A. C. M., Duarte, E. L., Lamy, M. T. M., Pasqualoto, K. F. M., & Sampaio, S. C. (2025). Formyl Peptide Receptors 1 and 2: Essential for Immunomodulation of Crotoxin in Human Macrophages, Unrelated to Cellular Entry. Cells, 14(15), 1159. https://doi.org/10.3390/cells14151159

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