Prospective study of neutrophil chemokine responses in trauma patients at risk for pneumonia.
Neutrophil hyperactivity contributes to organ failure, whereas hypofunction permits sepsis. The chemokine receptors CXCR1 and CXCR2 are central to polymorphonuclear neutrophil (PMN) function. We prospectively assessed CXCR function and expression in PMNs from trauma patients at high risk for pneumonia and their matched volunteer controls. CXCR2-specific calcium flux and chemotaxis were desensitized by injury, returning toward normal after 1 week. CXCR1 responses were relatively maintained. These defects appeared to be caused by preferential suppression of CXCR2 surface expression. To evaluate potential mechanisms of in vivo chemokine receptor regulation further we studied cross-desensitization of chemokine receptors in normal PMNs. Susceptibility to desensitization was in the order CXCR2 > CXCR1 > formyl peptide or C5a receptors. Trauma desensitizes CXC receptors, with CXCR2 being especially vulnerable. Desensitization is most marked immediately postinjury, generally resolving by Day 7. High-affinity chemoattractant receptors responsible for PMN chemotaxis from bloodstream to tissue appear to be regulated by injury. Receptors for end-target chemoattractants regulate CXCR1 and CXCR2 but resist suppression themselves and respond normally after injury. CXCR2 desensitization occurs before pneumonia, which developed in 44% of these patients. Suppression of high-affinity PMN receptors, like CXCR2, may predispose to pneumonia after trauma or other inflammatory conditions that lead to systemic inflammatory response syndrome.
Tarlowe
Michael H
MH
Division of Trauma, UMD/New Jersey Medical School, Department of Surgery, MSB G-592, 185 South Orange Avenue, Newark, NJ 07103, USA.
Duffy
Andrew
A
Kannan
Kollenkode B
KB
Itagaki
Kiyoshi
K
Lavery
Robert F
RF
Livingston
David H
DH
Bankey
Paul
P
Hauser
Carl J
CJ
D000293:Adolescent; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D016022:Case-Control Studies; D002478:Cells, Cultured; D019743:Chemokines, CXC / Q000032:analysis / Q000378:metabolism*; D002630:Chemotactic Factors; D002634:Chemotaxis, Leukocyte / Q000502:physiology; D004198:Disease Susceptibility; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000166:cytology* / Q000502:physiology; D011014:Pneumonia / Q000209:etiology* / Q000503:physiopathology; D011336:Probability; D011446:Prospective Studies; D019707:Receptors, Chemokine / Q000032:analysis / Q000378:metabolism*; D012016:Reference Values; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D013050:Spectrometry, Fluorescence; D013997:Time Factors; D014193:Trauma Centers
D019743:Chemokines, CXC; D002630:Chemotactic Factors; D019707:Receptors, Chemokine