期刊
BIOFACTORS
卷 39, 期 3, 页码 304-314出版社
WILEY
DOI: 10.1002/biof.1071
关键词
falciparum malaria; hemozoin (HZ); human monocytes; lysozyme; 15-(S; R)-hydroxy-6; 8; 11; 13-eicosatetraenoic acid (15-HETE)
资金
- Universita degli studi di Torino
- Azienda Sanitaria Locale-19 (ASL-19)
Natural hemozoin (nHZ), a lipid-bound ferriprotoporphyrin IX crystal produced by Plasmodium parasites after hemoglobin catabolism, seriously compromises the functions of human monocytes, and 15-hydroxyeicosatetraenoic acid (15-HETE) and 4-hydroxynonenal (4-HNE), two nHZ lipoperoxidation products, have been related to such a functional impairment. nHZ was recently shown to promote inflammation-mediated lysozyme release from human monocytes through p38 mitogen-activated protein kinase- (MAPK)- and nuclear factor (NF)-B-dependent mechanisms. This study aimed at identifying the molecule of nHZ lipid moiety that was responsible for these effects. Results showed that 15-HETE mimicked nHZ effects on lysozyme release, whereas 4-HNE did not. 15-HETE-enhanced lysozyme release was abrogated by anti-TNF- and anti-IL-1-blocking antibodies and mimicked by recombinant cytokines; on the contrary, MIP-1/CCL3 was not involved as a soluble mediator of 15-HETE effects. Moreover, 15-HETE early activated p38 MAPK and NF-B pathways by inducing p38 MAPK phosphorylation; cytosolic I-B phosphorylation and degradation; NF-B nuclear translocation and DNA-binding. Inhibition of both routes through chemical inhibitors (SB203580, quercetin, artemisinin, and parthenolide) prevented 15-HETE-dependent lysozyme release. Collectively, these data suggest that 15-HETE plays a major role in nHZ-enhanced monocyte degranulation. (c) 2013 BioFactors, 2013
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