Role of 15-hydroxyeicosatetraenoic acid in hemozoin-induced lysozyme release from human adherent monocytes.
Biofactors
; 39(3): 304-14, 2013.
Article
en En
| MEDLINE
| ID: mdl-23355332
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)-κB-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-α and anti-IL-1ß-blocking antibodies and mimicked by recombinant cytokines; on the contrary, MIP-1α/CCL3 was not involved as a soluble mediator of 15-HETE effects. Moreover, 15-HETE early activated p38 MAPK and NF-κB pathways by inducing p38 MAPK phosphorylation; cytosolic I-κBα phosphorylation and degradation; NF-κB 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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Monocitos
/
Muramidasa
/
Ácidos Hidroxieicosatetraenoicos
/
Hemoproteínas
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Biofactors
Asunto de la revista:
BIOQUIMICA
Año:
2013
Tipo del documento:
Article
País de afiliación:
Italia
Pais de publicación:
Países Bajos