RT Journal
A1 Williams MA, Cave CM, Quaid G, Solomkin JS
T1 CHemokine regulation of neutrophil function in surgical inflammation
JF Archives of Surgery
JO Archives of Surgery
YR 1999
FD December 1
VO 134
IS 12
SP 1360
OP 1366
DO 10.1001/archsurg.134.12.1360
UL http://dx.doi.org/10.1001/archsurg.134.12.1360
AB Background 
    Morbidity and even mortality correlate closely with major injury that causes a systemic inflammatory response. Cytokines and bioactive molecules present at the inflammatory site induce this response and regulate neutrophil proinflammatory responses. The CXC chemokines, important for neutrophil recruitment and activation, include interleukin 8 (IL-8), granulocyte chemotactic protein 2 (GCP-2), and epithelial cell-derived neutrophil attractant 78 (ENA-78). They induce neutrophil responses via 2 cell-surface receptors, CXCR-1 and CXCR-2. All 3 chemokines bind CXCR-2 with high affinity. Only IL-8 and GCP-2 bind CXCR-1 with high affinity.Hypothesis 
    The CXC chemokines regulate neutrophil responses differently.Methods 
    Pretreatment of neutrophils from healthy volunteers with IL-8, GCP-2, or ENA-78; measured IL-8–induced migration; and tumor necrosis factor α (TNF-α)–induced peroxide production.Results 
    Flow cytometry and radioligand binding data indicate that IL-8, GCP-2, and ENA-78 equivalently reduced CXCR-1 and CXCR-2 cell surface expression by 34% to 54%. All treatments decreased affinity of both receptors 1.5- to 2-fold. However, only IL-8 pretreatment inhibited chemotaxis to 10-nmol/L IL-8 (mean ± SE inhibition, 62% ± 6%). Although IL-8 and GCP-2, but not ENA-78, suppressed TNF-α–induced oxidant production (mean ± SE inhibition, 42% ± 8% and 40% ± 23%, respectively), only GCP-2 inhibited the oxidative response to complement fragment C5a, and to the bacterial cell wall peptide N-formyl-methionyl-leucyl-phenylalanine.Conclusions 
    The CXC chemokines regulate neutrophil proinflammatory functions differently. A thorough understanding of mechanisms for modulating neutrophil responses in inflammation will aid the development of interventions that reduce morbidity and mortality associated with severe trauma and sepsis.