title: G-protein receptor responses in trauma neutrophils.
abstract: BACKGROUND
  Trauma modulates polymorphonuclear neutrophil (PMN) function, predisposing to organ failure and infection. Many chemoattractants released by injury activate PMNs via G-protein-coupled (GPC) receptors, which elevate 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 +/- 3, 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 exposed to interleukin-8 (IL-8), growth regulated oncogene-alpha (GRO-alpha), and platelet-activating factor (PAF) to stimulate the CXCR1, CXCR2, and PAF receptors. [Ca2+]i flux measurements were used to quantify receptor responses. Receptor responses to individual as well as serial GPC agonists were studied over the week after injury and compared with the responses of PMNs from healthy volunteers (n = 10-23). Results were evaluated by one-way analysis 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 lowest on day 1, to peak on day 3, and to decrease again by day 7, but variations in response to GRO-alpha were the most marked (p < 0.03, analysis of variance). Whereas GRO-alpha primed IL-8 and IL-8 primed PAF in normal PMNs, GRO-alpha paradoxically suppressed IL-8 responses and IL-8 suppressed PAF responses in trauma PMNs. PAF priming of IL-8 responses was unaffected by injury.
  
  
  CONCLUSIONS
  Receptor responses to individual GPC agonists are suppressed early after trauma, but increase by day 3. Normal chemokine priming of PMN calcium 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 function while simultaneously suppressing others.
authors.affiliation: Department of Surgery, UMDNJ-New Jersey Medical School, Newark 07103, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Adams
authors.forename: C J
authors.initials: CJ
authors.lastname: Hauser
authors.forename: Z
authors.initials: Z
authors.lastname: Fekete
authors.forename: D H
authors.initials: DH
authors.lastname: Livingston
authors.forename: E A
authors.initials: EA
authors.lastname: Deitch
mesh_terms: D000328:Adult; D019540:Area Under Curve; D002118:Calcium / Q000378:metabolism; D016022:Case-Control Studies; D054360:Chemokine CXCL1; D019743:Chemokines, CXC; D002630:Chemotactic Factors / Q000235:genetics / Q000494:pharmacology; D005260:Female; D006133:Growth Substances / Q000235:genetics / Q000494:pharmacology; D006801:Humans; D015601:Injury Severity Score; D036341:Intercellular Signaling Peptides and Proteins; D016209:Interleukin-8 / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D010972:Platelet Activating Factor / Q000494:pharmacology; D010980:Platelet Membrane Glycoproteins / Q000187:drug effects / Q000378:metabolism; D011956:Receptors, Cell Surface; D018121:Receptors, Cytokine / Q000187:drug effects / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled; D023062:Receptors, Interleukin-8A / Q000187:drug effects / Q000378:metabolism; D023063:Receptors, Interleukin-8B / Q000187:drug effects / Q000378:metabolism; D013050:Spectrometry, Fluorescence; D014947:Wounds and Injuries / Q000097:blood / Q000276:immunology*
chemical_list: C475829:CXCL1 protein, human; D054360:Chemokine CXCL1; D019743:Chemokines, CXC; D002630:Chemotactic Factors; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D016209:Interleukin-8; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D018121:Receptors, Cytokine; D043562:Receptors, G-Protein-Coupled; D023062:Receptors, Interleukin-8A; D023063:Receptors, Interleukin-8B; C039351:platelet activating factor receptor; D002118:Calcium