Cytokine and adhesion molecule requirements for neutrophil recruitment during glycogen-induced peritonitis

Abstract.

Objective: Requirements for cytokines and adhesion molecules for perititoneal neutrophil recruitment during glycogen-induced peritonitis in rats were systematically defined.¶Subjects: 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, β₁ (VLA-4) and β₂ integrins (LFA-1 and Mac-1), ICAM-1, and the cytokines TNFα, IL-1 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%, 59% 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 43%, 40% and 62%, respectively. Unexpectedly, blockade of TNFα had no effect.¶Conclusions: These studies identify requirements for selectins, β₂ 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 TNFα suggests organ-specific cytokine and adhesion molecule requirements for neutrophil recruitment.