Attenuation of LPS-induced neutrophil thromboxane b2 release and chemiluminescence

J Cell Physiol. 1991 Feb;146(2):264-9. doi: 10.1002/jcp.1041460211.

Abstract

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 B2 (TXB2) 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 TXB2 release and oxygen free radical production. PMN TXB2 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 TXB2 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 TXB2 release whereas PTX and adenosine do not; 4) TBN significantly reduces PMA-induced PMN TXB2 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 TXB2 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine / pharmacology
  • Bucladesine / pharmacology
  • Humans
  • In Vitro Techniques
  • Lipopolysaccharides / pharmacology*
  • Luminescent Measurements
  • Neutrophils / drug effects*
  • Neutrophils / metabolism
  • Pentoxifylline / pharmacology
  • Terbutaline / pharmacology
  • Tetradecanoylphorbol Acetate / pharmacology
  • Thromboxane B2 / metabolism*
  • Tumor Necrosis Factor-alpha / physiology

Substances

  • Lipopolysaccharides
  • Tumor Necrosis Factor-alpha
  • Thromboxane B2
  • Bucladesine
  • Adenosine
  • Terbutaline
  • Tetradecanoylphorbol Acetate
  • Pentoxifylline