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C –Reactive Protein induces Leukocyte‐ Derived Myeloperoxidase in‐vitro and in‐vivo
Author(s) -
Singh Uma,
Devaraj Sridevi,
Jialal Ishwarlal
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a747
Subject(s) - myeloperoxidase , inflammation , in vivo , chemistry , in vitro , c reactive protein , cd16 , immunology , reactive oxygen species , biochemistry , biology , cd3 , cd8 , microbiology and biotechnology , antigen
Inflammation and oxidative stress play an important part in atherogenesis. C‐reactive protein (CRP), the prototypic marker of inflammation, mediates the progression of atherosclerosis. Leukocyte‐derived myeloperoxidase (MPO) catalyzes the formation of reactive oxygen species. Elevated levels of MPO and CRP are associated with acute coronary syndrome. Thus, we aimed to examine the effect of CRP on leukocyte‐derived MPO release. Human neutrophils/monocytes were isolated from peripheral blood by density gradient centrifugation followed by negative magnetic selection. PMN/monocytes were treated with CRP (0 & 25 ug/ml) for 6 hrs. MPO induction was measured as total mass and activity in culture supernatants. CRP treatment significantly induced (p<0.05) MPO release in both cell types. The effect was due to CRP per se as boiled CRP failed to induce MPO and polymyxin B had no effect on CRP‐induced MPO. CRP also caused intracellular (IC) MPO accumulation and nitration of IC proteins as well as of LDL incubated with both cell types. The mechanistic event was activation of p38 MAP kinase and NFkB in monocytes. CRP‐induced MPO release was via upregulation of CD16 in neutrophils and CD32 in monocytes. Also, human CRP injection in sterile pouch model of rats induced MPO in pouch exudates thus confirming our in‐vitro data of CRP‐induced MPO. We conclude that CRP induces another pro‐inflammatory phenotype via causing MPO release in vivo and in‐vitro system.