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.