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TNF‐α stimulates increased plasma membrane guanine nucleotide binding protein activity in polymorphonuclear leukocytes
Author(s) -
Klein Jon B.,
Scherzer Janice A.,
Harding George,
Jacobs Alfred A.,
McLeish Kenneth R.
Publication year - 1995
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.57.3.500
Subject(s) - pertussis toxin , chemotaxis , formyl peptide receptor , receptor , g protein , tumor necrosis factor alpha , biology , cholera toxin , phospholipase a2 , phospholipase c , microbiology and biotechnology , endocrinology , medicine , biochemistry , enzyme
TNF‐α enhances the response of polymorphonuclear leukocytes (PMN) to chemoattractants: however, the mechanism by which this occurs is unclear. We addressed the hypothesis that TNF‐α enhances the PMN response to chemoattractants by increasing chemoattractant receptor transmembrane signaling, using fMLP as the model chemoattractant. fMLP‐stimulated guanine nucleotide binding (G) protein activation was significantly increased in plasma membranes isolated from PMNs exposed to TNF‐α 100 U/ml for 10 minutes (TNF‐M), compared to membranes from control cells (CM). Formyl peptide receptor number and affinity were not significantly different in CM and TNF‐M. G i and G 3 content were increased in TNF‐M as measured by pertussis toxin and cholera toxin (CT) catalyzed ADP‐ribosylation, respectively. The increased G i was coupled to the formyl peptide receptor as shown by receptor‐specific CT labeling of G i . Immunoblot analysis showed that both G αi2 and G α3 were increased in TNF‐M. The functional activity of the increased G protein content was demonstrated by increased NaF‐stimulated phospholipase D activity in TNF‐α‐treated PMNs. We conclude that TNF‐α rapidly stimulates increased PMN plasma membrane expression of G proteins that couple formyl peptide receptors to effector enzymes. Regulation of G protein expression may be a significant mechanism by which TNF regulates PMN function. J. Leukoc. Biol . 57: 500–506; 1995.