Premium
Conversion of cardiac myocytes to a proinflammtory phenotype in sepsis: role of peroxynitrite derived from eNOS
Author(s) -
Rui Tao,
Stetsenko Inna,
Martin Claudio,
Kvietys Peter R.
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.a772
Subject(s) - peroxynitrite , myocyte , proinflammatory cytokine , enos , sepsis , chemistry , medicine , inflammation , immunology , endocrinology , nitric oxide , biochemistry , nitric oxide synthase , superoxide , enzyme
Isolated 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 peroxynitrite derived from eNOS in the sepsis‐induced conversion of cardiac myocytes to a proinflammatory phenotype. Sepsis was induced by i.p. injection of feces; saline (i.p.) served as a sham treatment. Cardiac myocytes were treated with plasma isolated from either sham or septic mice. Intracellular peroxynitrite (DHR oxidation) was increased in myocytes conditioned with septic plasma; an event prevented by a NOS inhibitor (L‐NAME). Supernatants from cardiac myocytes conditioned with septic plasma increased PMN transendothelial migration; an event prevented by L‐NAME or a peroxynitrite decomposition catalyst, Fe‐TPPs. Supernatants obtained from cardiac myocytes conditioned with septic plasma had higher levels of the chemokines, LIX and KC than those treated with sham plasma. Supernatanats obtained from the eNOS−/− myocytes conditioned with septic plasma 1) failed to promote PMN migration and 2) contained less LIX and KC than their wild type counterparts. Collectively, these findings indicate peroxynitrite derived from eNOS plays an important role in the conversion of cardiac myocytes to a proinflammatory phenotype in sepsis. (CIHR MOP‐81303, MOP‐13668 and MGC 12816)