Cytokine and adhesion molecule requirements for neutrophil recruitment during glycogen-induced peritonitis.
OBJECTIVE
Requirements for cytokines and adhesion molecules for peritoneal neutrophil recruitment during glycogen-induced peritonitis in rats were systematically defined.


METHODS
Male Long Evans rats (275-300 g).


METHODS
Four hours after intraperitoneal injection of 25 mg oyster glycogen, neutrophilic exudates were harvested. Effects of blocking reagents (injected intravenously) to rat E-, L- and P-selectins, beta1 (VLA-4) and beta2 integrins (LFA-1 and Mac-1), ICAM-1, and the cytokines TNFalpha, IL- and IL-8 were assessed.


RESULTS
Administration of synthetic sialyl Lewis(x) oligosaccharide reduced neutrophil recruitment to the peritoneum by 26%. Antibody to E-selectin reduced neutrophil accumulation by 71%, while anti-L-selectin reduced neutrophil accumulation by 59%, and anti-P-selectin was without an effect. Similar patterns of inhibition were found when selectin-Ig chimeras were employed. Antibodies to LFA-1 (CD11a), Mac-1 (CD11b) or CD18 reduced neutrophil accumulation by 62 percent, 59 percent and 86%, respectively, while anti-VLA-4 was without effect. Anti-ICAM-1 reduced cell influx by 65%. IL-1 receptor antagonist and antibodies to IL-1 and human IL-8 reduced neutrophil accumulation by 43alpha, 40% and 62 percent, respectively. Unexpectedly, blockade of TNFalpha had no effect.


CONCLUSIONS
These studies identify requirements for selectins, beta2 integrins, IL-1 and a rat chemokine(s) similar to human IL-8 for neutrophil recruitment during glycogen-induced peritonitis. The lack of participation of VLA-4, P-selectin and TNFalpha suggests organ-specific cytokine and adhesion molecule requirements for neutrophil recruitment.
Department of Pathology, The University of Michigan Medical School, Ann Arbor 48109-0602, USA.
M S
MS
Mulligan
A B
AB
Lentsch
M
M
Miyasaka
P A
PA
Ward
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D018821:CD18 Antigens / Q000276:immunology / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000502:physiology*; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000502:physiology*; D019040:E-Selectin / Q000276:immunology / Q000502:physiology; D006003:Glycogen; D006801:Humans; D019012:Integrin beta1 / Q000276:immunology / Q000502:physiology; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology / Q000502:physiology; D019041:L-Selectin / Q000276:immunology / Q000502:physiology; D008297:Male; D019007:P-Selectin / Q000276:immunology / Q000502:physiology; D010529:Peritoneal Cavity / Q000473:pathology; D010538:Peritonitis / Q000139:chemically induced* / Q000473:pathology*; D051381:Rats
D000906:Antibodies; D018821:CD18 Antigens; D015815:Cell Adhesion Molecules; D016207:Cytokines; D019040:E-Selectin; D019012:Integrin beta1; D019007:P-Selectin; D018799:Intercellular Adhesion Molecule-1; D019041:L-Selectin; D006003:Glycogen