G-protein receptor responses in trauma neutrophils

Background: Trauma modulates polymorphonuclear neutrophil (PMN) function, p redisposing to organ failure and infection. Many chemoattractants released by injury activate PMNs via G-protein-coupled (GPC) receptors, which elevat e PMN cytosolic calcium ([Ca2+](i)). Nonetheless, PMN GPC receptor function after injury is unstudied. Methods: PMNs from 11 major trauma patients (Injury Severity Score = 31 +/- 31 eight men and three women, age = 38 +/- 3) were obtained on days 1, 3, and 7 after injury. Nine developed organ failure and one died. PMNs were ex posed to interleukin-8 (IL-8), growth regulated oncogene-alpha (GRO-alpha), and platelet-activating factor (PAF) to stimulate the CXCR1, CXCR2, and PA F receptors, [Ca2+](i) flux measurements were used to quantify receptor res ponses. Receptor responses to individual as well as serial GPC agonists wer e studied over the week after injury and compared with the responses of PMN s from healthy volunteers (n = 10-23), Results were evaluated by one-way an alysis of variance, and paired and unpaired t tests. Results: Responses to GRO-alpha and PAF were significantly depressed early after injury (p < 0.01), Responses to all agonists tested tended to be lowe st on day 1, to peak on day 3, and to decrease again by day 7, but variatio ns in response to GRO-<alpha> were the most marked (p < 0.03, analysis of v ariance). Whereas GRO-<alpha> primed IL-8 and IL-8 primed PAF in normal PMN s, GRO-alpha paradoxically suppressed IL-8 responses and IL-8 suppressed PA F responses in trauma PMNs, PAF priming of IL-8 responses was unaffected by injury, Conclusion: Receptor responses to individual GPC agonists are suppressed ea rly after trauma, but increase by day 3, Normal chemokine priming of PMN ca lcium mobilization is reversed by injury; priming by PAF is intact. PMN GPC responses depend on the sequence in which agonists are encountered. Injury appears to alter these interactions, thus priming some aspects of PMN func tion while simultaneously suppressing others.