Altered calcium regulation and function of human neutrophils during multiple trauma.
Altered intracellular Ca2+ concentration is a pivotal regulatory mechanism of leukocyte function. Since polymorphonuclear neutrophils (PMN) are involved in traumatic organ dysfunction, we prospectively investigated Ca2+ regulation and function of circulating PMN multiple trauma patients (Group A: ISS < 27; Group B: ISS > or = 27). Circulating PMN were isolated during 12 days, followed by determination of formyl-methionyl-leucyl-phenylalanine (fMLP)-induced PMN-superoxide production (PMN-SOP) by SOD-inhibitable ferricytochrome C reduction, and PMN cytosolic Ca2+ concentration ([Ca2+]i) by fluorescent fura2/AM (340/380 ratio). PMN-SOP was significantly higher in Group B (mean ISS: 39.9 +/- 2; n = 21) at day of admission than in controls and Group A (mean ISS: 18.2 +/- 1; n = 22) (P< 0.05). In Group B, the significant rise of basal [Ca2+]i between Day 2 and Day 4 was associated with significant lower PMN-SOP during that period (P < 0.05). The fMLP-induced [Ca2+]i response was supranormal in both groups. PMN-elastase concentrations were substantially higher in Group B compared with Group A until Day 4. Circulating IL-6, IL-8, and soluble TNF-receptor (55 kD) were significantly increased in Group B compared with Group A at the day of trauma (P < 0.05). Severe trauma is characterized by a biphasic pattern of neutrophil priming characterized by early increase and secondary suppression. The association of depressed neutrophil superoxide production (deactivation) and elevated basal [Ca2+]i suggests Ca2+-mediated disturbance of neutrophil NADPH-oxidase metabolism.
Rose
S
S
University of Saarland, Department of Trauma, Hand and Reconstructive Surgery, Homburg/Saar, Germany.
Illerhaus
M
M
Wiercinski
A
A
Mutschler
W
W
Marzi
I
I
D000328:Adult; D002118:Calcium / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D005260:Female; D005979:Glutathione Peroxidase / Q000097:blood; D006801:Humans; D015994:Incidence; D018836:Inflammation Mediators / Q000378:metabolism; D015601:Injury Severity Score; D019272:Leukocyte Elastase / Q000097:blood; D008054:Lipid Peroxides / Q000097:blood; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D009102:Multiple Organ Failure / Q000453:epidemiology / Q000276:immunology; D009104:Multiple Trauma / Q000276:immunology*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D018375:Neutrophil Activation / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism*; D009195:Peroxidase / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism
D018836:Inflammation Mediators; D008054:Lipid Peroxides; D013481:Superoxides; D008315:Malondialdehyde; D009240:N-Formylmethionine Leucyl-Phenylalanine; D009195:Peroxidase; D005979:Glutathione Peroxidase; D019272:Leukocyte Elastase; D002118:Calcium