Preferential loss of CXCR-2 receptor expression and function in patients who have undergone trauma.
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.
Quaid
G A
GA
Department of Surgery, University of Cincinnati College of Medicine, Ohio 45267-0558, USA. chickgq@aol.com
Cave
C
C
Robinson
C
C
Williams
M A
MA
Solomkin
J S
JS
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
D016209:Interleukin-8; D019707:Receptors, Chemokine; D014409:Tumor Necrosis Factor-alpha; D009240:N-Formylmethionine Leucyl-Phenylalanine; D015936:Complement C5a; D002118:Calcium