• G Quaid, M Williams, C Cave, and J Solomkin.
• Department of Surgery, College of Medicine, University of Cincinnati, Cincinnati, OH 45267-0558, USA. chickgq@aol.com
• J Trauma. 2001 Sep 1;51(3):446-51.

BackgroundPrimed neutrophils are thought to play a key role in inflammatory pathology. We have shown though in vitro studies that interleukin (IL)-8 and growth-related oncogene-alpha (GROalpha) (CXCR2-specific chemokines) regulate the respiratory burst via the CXCR2 receptor. We have also shown in vivo, CXCR2 receptors are down-regulated in severely injured patients. Our hypothesis is that regulation of the respiratory burst by CXCR2 is lost after severe injury.MethodsPatient neutrophils were studied within 24 hours of admission to the hospital; excluded were severe head injury and patients with Injury Severity Score < 16. Patient and normal neutrophils were isolated by Ficoll-Hypaque centrifugation after dextran sedimentation. Neutrophils were plated with buffer, 50 nmol/L IL-8 or GROalpha on fibronectin-coated plates for 15 minutes, then stimulated with 10 ng/mL of TNFalpha. CXCR2 expression was measured by flow cytometry. Receptor function was assessed by calcium mobilization.ResultsOne female and 10 male patients with an average age of 37 +/- 3 and Injury Severity Score of 24 +/- 5 suffered blunt injury. CXCR2 showed a 32% +/- 7% loss, whereas CXCR1 showed 15% +/- 6% reduction. GROalpha stimulation of patient neutrophils showed 60% +/- 16% decrease in calcium mobilization, whereas IL-8 showed no decline. At 40 minutes, IL-8 and GROalpha significantly inhibited TNFalpha adherence-dependent peroxide production in normal neutrophils (35% +/- 4% and 45% +/- 3%, respectively; p < 0.05). Both IL-8 and GROalpha lost the ability to suppress the respiratory burst in severely injured patients, but GROalpha had a significantly greater loss of this suppression (p = 0.004).ConclusionIL-8 and GROalpha lose the ability to regulate the TNFalpha-induced respiratory burst. This may contribute to neutrophil dysregulation after injury and result in organ injury.

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