title: Disparate signal transduction in neutrophil CD18 adhesion receptor expression versus superoxide generation.
abstract: BACKGROUND
  We have previously shown that platelet-activating factor (PAF) primes polymorphonuclear neutrophils (PMNs) for superoxide generation and, concurrently, increases CD11/CD18 receptor expression; both events appear central to the pathogenesis of postinjury multiple organ failure. Recently, the counterinflammatory role of the neuroendocrine response to trauma has been emphasized, and, specifically, beta-adrenergic stimulation has been found to inhibit PMN activation.
  
  
  METHODS
  Normal human PMNs were primed with PAF (10(-9) mol/L for 5 minutes) or pretreated with beta-receptor stimulation (isoproterenol, 10(-7) mol/L) or adenylate cyclase (AC) activation (forskoklin, 10(-7) mol/L) for 5 minutes and then primed with PAF. Superoxide generation in response to N-formyl-methionyl-leucyl-phenylalanine (10(-6) mol/L) was measured by superoxide dismutase inhibitable reduction of cytochrome C and CD18 expression determined by flow cytometry.
  
  
  RESULTS
  PAF primed PMNs for superoxide generation (229.5 +/- 42.3 nmol/10(6) cells/min versus 18.7 +/- 6.5), whereas pretreatment with beta-adrenoreceptor stimulation (112.9 +/- 20.6) or AC activation (115.3 +/- 12.6) dramatically attenuated this process (p < 0.0001). PAF also enhanced CD18 expression (6.1 +/- 1.1 mean fluorescence intensity versus 10.3 +/- 2.3), but beta-adrenoreceptor stimulation (10.1 +/- 2.1) and AC activation (9.7 +/- 1.9) had no discernible effect.
  
  
  CONCLUSIONS
  PAF priming of PMNs for superoxide generation was inhibited by the beta-adrenergic signal transduction pathway, but CD18 expression was not regulated via this pathway.
authors.affiliation: Department of Surgery, Denver General Hospital, CO 80204.
authors.forename: F J
authors.initials: FJ
authors.lastname: Kim
authors.forename: E E
authors.initials: EE
authors.lastname: Moore
authors.forename: F A
authors.initials: FA
authors.lastname: Moore
authors.forename: K
authors.initials: K
authors.lastname: Koike
authors.forename: V S
authors.initials: VS
authors.lastname: Carl
authors.forename: A
authors.initials: A
authors.lastname: Banerjee
mesh_terms: D000328:Adult; D006801:Humans; D016177:Macrophage-1 Antigen / Q000032:analysis*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism; D019255:NADPH Oxidases; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D010972:Platelet Activating Factor / Q000494:pharmacology; D015398:Signal Transduction; D013481:Superoxides / Q000378:metabolism*
chemical_list: D016177:Macrophage-1 Antigen; D010972:Platelet Activating Factor; D013481:Superoxides; D009240:N-Formylmethionine Leucyl-Phenylalanine; D009247:NADH, NADPH Oxidoreductases; D019255:NADPH Oxidases