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Lysophosphatidylcholines prime the NADPH oxidase and stimulate multiple neutrophil functions through changes in cytosolic calcium
Author(s) -
Silliman Christopher C.,
Elzi David J.,
Ambruso Daniel R.,
Musters Rene J.,
Hamiel Christine,
Harbeck Ronald J.,
Paterson Andrew J.,
Bjornsen A. Jason,
Wyman Travis H.,
Kelher Marguerite,
England Kelly M.,
McLaughlinMalaxecheberria Nathan,
Barnett Carlton C.,
Aiboshi Junichi,
Bannerjee Anirban
Publication year - 2003
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 - 10.1189/jlb.0402179
Subject(s) - degranulation , phosphorylation , biology , pertussis toxin , nadph oxidase , cytosol , receptor , tyrosine phosphorylation , chemotaxis , g protein , microbiology and biotechnology , medicine , endocrinology , biochemistry , enzyme , reactive oxygen species
A mixture of lysophosphatidylcholines (lyso‐PCs) are generated during blood storage and are etiologic in models of acute lung injury. We hypothesize that lyso‐PCs stimulate polymorphonuclear neutrophils (PMNs) through Ca 2 + ‐dependent signaling. The lyso‐PC mix (0.45–14.5 μM) and the individual lyso‐PCs primed formyl‐Met‐Leu‐Phe (fMLP) activation of the oxidase (1.8‐ to 15.7‐fold and 1.7‐ to 14.8‐fold; P <0.05). Labeled lyso‐PCs demonstrated a membrane association with PMNs and caused rapid increases in cytosolic Ca 2 + . Receptor desensitization studies implicated a common receptor or a family of receptors for the observed lyso‐PC‐mediated changes in PMN priming, and cytosolic Ca 2 + functions were pertussis toxin‐sensitive. Lyso‐PCs caused rapid serine phosphorylation of a 68‐kD protein but did not activate mitogen‐activated protein kinases or cause changes in tyrosine phosphorylation. With respect to alterations in PMN function, lyso‐PCs caused PMN adherence, increased expression of CD11b and the fMLP receptor, reduced chemotaxis, provoked changes in morphology, elicited degranulation, and augmented fMLP‐induced azurophilic degranulation ( P <0.05). Cytosolic Ca 2 + chelation inhibited lyso‐PC‐mediated priming of the oxidase, CD11b surface expression, changes in PMN morphology, and serine phosphorylation of the 68‐kD protein. In conclusion, lyso‐PCs affect multiple PMN functions in a Ca 2 + ‐dependent manner that involves the activation of a pertussis toxin‐sensitive G‐protein.