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 sig nal via 2 receptors, CXCR-1 and CXCR-2. In vitro studies have shown prefere ntial loss of CXCR-2 expression and function after exposure to interleukin 8, N-formyl-methionyl-leucyl-phenylalanine (fMLP), C5a, and tumor necrosis factor alpha. Hypothesis: CXCR-2 expression and function are preferentially down-regulate d in severely injured patients. Methods: We studied 20 patients within 24 hours of admission to the hospita l. 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 mobil ization and neutrophil migration to 10 nmol of interleukin 8, growth-relate d on cogene alpha, and fMLP was measured to determine receptor function. Results: Compared with CXCR-1, there is a greater loss of CXCR-2 receptor e xpression in the severely injured group (P =.01). Neutrophils from patients with Injury Severity Scores greater than 16 did not mobilize calcium in re sponse to growth-related oncogene cr. 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-regulat ed in severely injured patients. Our data suggest that there are multiple m echanisms, in addition to receptor down-regulation, that play a role in the loss of migration and calcium flux in human neutrophils after injury.