title: Preferential loss of CXCR-2 receptor expression and function in patients who have undergone trauma.
abstract: BACKGROUND
  In response to traumatic injury or infection, human neutrophils are directed to the site of injury or infection by CXC chemokines that signal via 2 receptors, CXCR-1 and CXCR-2. In vitro studies have shown preferential loss of CXCR-2 expression and function after exposure to interleukin 8, N-formyl-methionyl-leucyl-phenylalanine (fMLP), C5a, and tumor necrosis factor alpha.
  
  
  OBJECTIVE
  CXCR-2 expression and function are preferentially down-regulated in severely injured patients.
  
  
  METHODS
  We studied 20 patients within 24 hours of admission to the hospital. Patients with head injuries were excluded. Injury Severity Scores (range, 1-50; mean, 35) were calculated for each patient. To determine expression of CXCR-1 and CXCR-2, flow cytometry was used. Intracellular calcium mobilization and neutrophil migration to 10 nmol of interleukin 8, growth-related oncogene alpha, and fMLP was measured to determine receptor function.
  
  
  RESULTS
  Compared with CXCR-1, there is a greater loss of CXCR-2 receptor expression in the severely injured group (P = .01). Neutrophils from patients with Injury Severity Scores greater than 16 did not mobilize calcium in response to growth-related oncogene alpha. However, there was no loss of calcium mobilization to interleukin 8 or fMLP. Chemotaxis to various stimulants is decreased in all injury groups.
  
  
  CONCLUSIONS
  CXCR-2 expression and function are preferentially down-regulated in severely injured patients. Our data suggest that there are multiple mechanisms, in addition to receptor down-regulation, that play a role in the loss of migration and calcium flux in human neutrophils after injury.
authors.affiliation: Department of Surgery, University of Cincinnati College of Medicine, Ohio 45267-0558, USA. chickgq@aol.com
authors.forename: G A
authors.initials: GA
authors.lastname: Quaid
authors.forename: C
authors.initials: C
authors.lastname: Cave
authors.forename: C
authors.initials: C
authors.lastname: Robinson
authors.forename: M A
authors.initials: MA
authors.lastname: Williams
authors.forename: J S
authors.initials: JS
authors.lastname: Solomkin
mesh_terms: D000293:Adolescent; D000328:Adult; D002118:Calcium / Q000502:physiology; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D015936:Complement C5a / Q000502:physiology; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression / Q000502:physiology; D006801:Humans; D015601:Injury Severity Score; D016209:Interleukin-8 / Q000502:physiology; D008297:Male; D008875:Middle Aged; D009104:Multiple Trauma / Q000235:genetics / Q000276:immunology*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000276:immunology; D020556:Neutrophil Infiltration / Q000276:immunology; D019707:Receptors, Chemokine / Q000235:genetics*; D018746:Systemic Inflammatory Response Syndrome / Q000235:genetics / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
chemical_list: D016209:Interleukin-8; D019707:Receptors, Chemokine; D014409:Tumor Necrosis Factor-alpha; D009240:N-Formylmethionine Leucyl-Phenylalanine; D015936:Complement C5a; D002118:Calcium