PKC-α is involved in the signaling of phagocytosis induced by two snake venom secretory PLA 2 S in macrophages.

Autor: Zuliani JP; Laboratório de Farmacologia - Instituto Butantan, São Paulo, Brazil; Laboratório de Imunologia Celular Aplicada à Saúde, Fundação Oswaldo Cruz Rondônia/FIOCRUZ-RO, Porto Velho, RO, Brazil; Dep. Medicina, Universidade Federal de Rondônia, UNIR, Porto Velho, RO, Brazil. Electronic address: juliana.zuliani@fiocruz.br., Yamanouye N; Laboratório de Farmacologia - Instituto Butantan, São Paulo, Brazil. Electronic address: norma@butantan.gov.br., Gutiérrez JM; Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica., Teixeira C; Laboratório de Farmacologia - Instituto Butantan, São Paulo, Brazil. Electronic address: catarina.teixeira@butantan.gov.br.
Jazyk: angličtina
Zdroj: Toxicon : official journal of the International Society on Toxinology [Toxicon] 2024 Aug 28; Vol. 247, pp. 107824. Date of Electronic Publication: 2024 Jun 20.
DOI: 10.1016/j.toxicon.2024.107824
Abstrakt: Phagocytosis, an essential process for host defense, requires the coordination of a variety of signaling reactions. MT-II, an enzymatically inactive Lys49 phospholipase A 2 (PLA 2 ) homolog, and MT-III, a catalytically-active Asp49 PLA 2 , are known to activate phagocytosis in macrophages. In this study, the signaling pathways mediating phagocytosis, focusing on protein kinases, were investigated. Macrophages from male Swiss mice peritoneum were obtained 96 h after intraperitoneal thioglycolate injection. Phagocytosis was evaluated using non-opsonized zymosan particles in the presence or absence of specific inhibitors, as well as PKC and PKC-α localization by confocal microscopy. Moreover, protein kinase C (PKC) activity was assessed by γP 32 ATP in macrophages stimulated by both PLA 2 s. Data showed that both sPLA 2 s increased phagocytosis. Cytochalasin D, staurosporine/H7, wortmannin, and herbimycin, inhibitors of actin polymerization, PKC, phosphoinositide 3-kinase (PI3K), and protein tyrosine kinase (PTK), respectively, significantly reduced phagocytosis induced by both PLA 2 s. PKC activity was increased in macrophages stimulated by both PLA 2 s. Actin polymerization and talin were evidenced by immunofluorescence and talin was recruited 5 min after both PLA 2 s stimulation. PKC and PKC-α localization within the cell were increased after 60 min of MT-II and MT-III stimulation. These data suggest that the effect of both PLA 2 s depends on actin cytoskeleton rearrangements and the activation of PKC, PI3K, and PTK signaling events required for phagocytosis.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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