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CRP Induces Superoxide Anion Release from Rat Macrophages In vivo Via Upregulation of NADPH oxidase
Author(s) -
Devaraj Sridevi,
Singh Uma,
dasu Mohan r
Publication year - 2008
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.22.1_supplement.48.12
Subject(s) - superoxide , nadph oxidase , in vivo , chemistry , oxidative stress , reactive oxygen species , pharmacology , downregulation and upregulation , biochemistry , microbiology and biotechnology , medicine , biology , enzyme , gene
C‐reactive protein (CRP), the prototypic marker of inflammation is a cardiovascular risk marker. Recent in vitro studies support a role for CRP in atherogenesis. CRP induces oxidative stress in vitro. However, there is a paucity of data examining effects of CRP on oxidative stress in vivo. Thus, we tested the effects of CRP in vivo administration on superoxide anion in a rat sterile air pouch model. Sterile air pouches were made on Male hooded Wistar rats (150 gm, n=5/group) by injecting 20ml sterile air. Human CRP, isolated from pleural fluid and purified of endotoxin/azide, (25ug/ml /intrapouch) or Human serum albumin (HA,25ug/mL) were injected. After 12 hours, blood and pouch exudates were used to assess superoxide production by DHE fluorescence and cytochrome C method. CRP treatment significantly increased DHE labeling and superoxide production in pouch macrophages (p<0.01). Also, CRP resulted in increased p47phox activity. Pretreatment with NADPH oxidase inhibitor, apocyanin significantly abrogated CRP‐induced superoxide anion release and DHE fluorescence (77% and 66% decrease, p<0.001). Pretreatment with ERK inhibitor, but not p38MAPK or JNK significantly decreased CRP induced superoxide in vivo (p<0.05). Thus, CRP induces superoxide production in vivo via upregulation of p47phox activity and ERK phosphorylation. This in vivo demonstration lends support to its role in atherothrombosis.