Secretory phospholipases A(2) induce beta-glucuronidase release and IL-6 production from human lung macrophages

Citation
M. Triggiani et al., Secretory phospholipases A(2) induce beta-glucuronidase release and IL-6 production from human lung macrophages, J IMMUNOL, 164(9), 2000, pp. 4908-4915
Citations number
63
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Immunology
Journal title
JOURNAL OF IMMUNOLOGY
ISSN journal
0022-1767 → ACNP
Volume
164
Issue
9
Year of publication
2000
Pages
4908 - 4915
Database
ISI
SICI code
0022-1767(20000501)164:9<4908:SPAIBR>2.0.ZU;2-W
Abstract
Secretory phospholipases A(2) (sPLA(2)s) are a group of extracellular enzym es that release fatty acids at the sn-2 position of phospholipids, Group II A sPLA(2) has been detected in inflammatory fluids, and its plasma level is increased in inflammatory diseases. To investigate a potential mechanism o f sPLA(2)-induced inflammation me studied the effect of group IA (from cobr a venom) and group IIA (human synovial) sPLA(2)s on human macrophages. Both sPLA(2)s induced a concentration- and Ca2+-dependent, noncytotoxic release of beta-glucuronidase (16.2 +/- 2.4% and 13.1 +/- 1.5% of the total conten t with groups IA and IIA, respectively). Both sPLA(2)s also increased the r ate of secretion of IL-6 and enhanced the expression of IL-6 mRNA. Preincub ation of macrophages with inhibitors of the hydrolytic activity of sPLA(2) or cytosolic PLA(2) did not influence the release of beta-glucuronidase. In cubation of macrophages with p-aminophenyl-mannopyranoside-BSA (mp-BSA), a ligand of the mannose receptor, also resulted in beta-glucuronidase release . However, while preincubation of macrophages with mp-BSA had no effect on beta-glucuronidase release induced by group IIA sPLA(2), it enhanced that i nduced by group IA sPLA(2). A blocking Ab anti-mannose receptor inhibited b oth mp-BSA-and group II-induced beta-glucuronidase release. Taken together, these data indicate that group IA and IIA sPLA(2)s activate macrophages wi th a mechanism independent from their enzymatic activities and probably rel ated to the activation of the mannose receptor or sPLA(2)-specific receptor s. The secretion of enzymes and cytokines induced by sPLA(2)s from human ma crophages may play an important role in inflammation and tissue damage asso ciated with the release of sPLA(2)s.