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Attenuation of LPS‐induced neutrophil thromboxane B 2 release and chemiluminescence
Author(s) -
Zheng Hui,
Crowley Jeffrey J.,
Chan Jane C.,
Raffin Thomas A.
Publication year - 1991
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1041460211
Subject(s) - chemistry , lipopolysaccharide , chemiluminescence , thromboxane , phorbol , pentoxifylline , arachidonic acid , adenosine , thromboxane a2 , thromboxane b2 , reactive oxygen species , nitric oxide , tumor necrosis factor alpha , medicine , endocrinology , pharmacology , platelet , protein kinase c , biochemistry , signal transduction , receptor , enzyme , organic chemistry
Polymorphonuclear leukocytes (PMN) may play a key role in acute lung injury and ARDS. The mechanisms of PMN‐mediated lung injury include the release of inflammatory mediators, such as oxygen free radicals which cause direct tissue injury, and arachidonic acid metabolites which cause pulmonary vasoconstriction and increased vascular permeability. The goals of this in vitro study were (1) to assess the effects of PMN‐activating agents (lipopolysaccharide, LPS; phorbol myristate acetate, PMA; tumor necrosis factor, TNF) on PMN thromboxane B 2 (TXB 2 ) release and oxygen free radical production and (2) to determine the effects of agents purported to suppress PMN activity (pentoxifylline, PTX; adenosine; dibutyryl cyclic AMP, DBcAMP; and terbutaline, TBN) on activator‐induced PMN TXB 2 release and oxygen free radical production. PMN TXB 2 release was determined by radioimmunoassay and oxygen free radical production was monitored by Chemiluminescence. Our results show that (1) LPS and PMA significantly increase PMN TXB 2 release, whereas tumor necrosis factor (TNF) has no effect; (2) LPS and PMA significantly increase PMN Chemiluminescence; (3) DBcAMP and TBN significantly reduce LPS‐induced PMN TXB 2 release whereas PTX and adenosine do not; (4) TBN significantly reduces PMA‐induced PMN TXB 2 release whereas other agents do not; (5)All agents(PTX, adenosine, DBcAMP, and TBN) significantly reduce LPS‐induced PMN Chemiluminescence but none attenuate PMA‐induced PMN Chemiluminescence. We conclude that:LPS and PMA activate PMN manifested by TXB 2 release and Chemiluminescence. Additionally, all the PMN suppressing agents do attenuate some PMN functions. Of interest, PTX, adenosine, DBcAMP, and TBN have different effects depending upon functional assay and activating agent. It will be important to investigate the mechanisms by which PMN suppressing agents alter signal transduction resulting in differential effects on PMN function.