Polymicrobial sepsis disrupts normal neutrophil extracellular matrix protein interactions.
The purpose of this study was to examine how intra-abdominal sepsis and extracellular matrix proteins (fibronectin, laminin) affect adherent polymorphonuclear leukocyte (PMN) function. Two groups of swine were studied: Group I (n = 5) underwent sham laparotomy; Group II (n = 8) underwent cecal ligation and incision. PMN adherent to either fibronectin (F) or laminin (L) had increased candicidal activity over buffer (B) by Group I but not by post-operative day 8 Group II PMN. (Percent specific release 51Cr-Group I--35.00, 68.25, 64.75% for B, F, and L; P less than 0.001 comparing B vs. F or L; Group II--14.25, 12.50, 12.75% for B, F, and L; P = NS comparing B vs. F or L.) To determine the mechanism for this finding, PMN priming was then assessed by evaluating both PMN adherence to extracellular matrix proteins and the cell surface expression of CR1/CR3 by using sheep RBC opsonized with C3b or C3bi. PMN activation was assayed by using MTT-Formazan, myeloperoxidase, and hypochlorous acid (HOCl) production. Fibronectin and laminin increased PMN adherence and CR1/CR3 expression over buffer by Group I and Group II animals. Fibronectin and laminin increased MTT-Formazan, myeloperoxidase, and HOCl production over buffer by Group I PMN but not POD 8 Group II PMN. These results suggest that untreated intra-abdominal sepsis partially abrogates the effect of extracellular matrix proteins on PMN function; in particular, the activation but not priming of adherent PMN by extracellular matrix proteins is reduced in this clinical situation.
Simms
H H
HH
Department of Surgery, Rhode Island Hospital/Brown University School of Medicine, Providence 02903.
D'Amico
R
R
D000818:Animals; D016470:Bacteremia / Q000276:immunology*; D002176:Candida albicans / Q000276:immunology; D002432:Cecum / Q000601:surgery; D002448:Cell Adhesion; D005260:Female; D005353:Fibronectins / Q000502:physiology*; D005562:Formazans / Q000378:metabolism; D006997:Hypochlorous Acid / Q000378:metabolism; D007797:Laminin / Q000502:physiology*; D008026:Ligation; D009504:Neutrophils / Q000276:immunology*; D009195:Peroxidase / Q000378:metabolism; D013552:Swine
D005353:Fibronectins; D005562:Formazans; D007797:Laminin; D006997:Hypochlorous Acid; D009195:Peroxidase