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Cardiac myocytes are a cellular source of chemokines in sepsis: role of NAD(P)H oxidase
Author(s) -
Rui Tao,
Martin Claudio,
Kvietys Peter R.
Publication year - 2006
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.20.4.a647-c
Subject(s) - nadph oxidase , proinflammatory cytokine , myocyte , apocynin , chemokine , sepsis , chemistry , immunology , medicine , inflammation , reactive oxygen species , biochemistry
Neutrophil accumulation within the heart during sepsis is an important contributing factor involved in sepsis‐induced myocardial dysfunction. We have previously shown that cardiac myocytes challenged with septic plasma are converted to a proinflammatory phenotype; these myocytes generate chemokines and promote neutrophil (PMN) transendothelial migration. The aim of present study was to assess the role of NADPH oxidase in the sepsis‐induced conversion of cardiac myocytes to a proinflammatory phenotype. Feces‐induced peritonitis (FIP) was used as murine sepsis model. Cardiac myocytes were treated with plasma isolated from either sham or septic mice. Supernatants collected from plasma‐conditioned cardiac myocytes were used for determination of chemokine production (ELISA) and PMN transendothelial migration (cell culture inserts). Cardiac myocyte NADPH oxidase activity increased after exposure of the cells to septic plasma (increased production of superoxide; lucigenin‐enhanced chemiluminesence). Supernatants from cardiac myocytes conditioned with septic plasma 1) contained higher levels of the chemokine, KC, and 2) increased PMN transendothelial migration. Both chemokine production and PMN migration were prevented when the myocytes were pretreated with NADPH oxidase inhibitors (diphenylene iodonium;10 μM or apocynin;1 mM) or when myocytes from mice deficient in gp 91phox were used. Collectively, these findings indicate that the NADPH oxidase signaling pathway plays an important role in the conversion of cardiac myocytes to a proinflammatory phenotype in sepsis. (CIHR MOP‐13668, MGC‐12816)