Antiinflammatory Effects of Soluble Complement Receptor Type 1 Promote Rapid Recovery of Ischemia/Reperfusion Injury in Rat Small Intestine

• Published in: Clinical immunology (Orlando, Fla.) Fla.), 1999-02, Vol.90 (2), p.266-275
• Main Authors: Eror, Alec T., Stojadinovic, Alexander, Starnes, Benjamin W., Makrides, Savvas C., Tsokos, George C., Shea-Donohue, Terez
• Format: Article
• Language: English
• Subjects: Animals; Anti-Inflammatory Agents, Non-Steroidal - isolation & purification; Anti-Inflammatory Agents, Non-Steroidal - therapeutic use; Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Complement Activation; Disease Models, Animal; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Hemodynamics; Intestinal Mucosa - blood supply; Intestinal Mucosa - injuries; Intestinal Mucosa - pathology; intestine; Intestine, Small - blood supply; Intestine, Small - injuries; Intestine, Small - pathology; ischemia/reperfusion; leukotriene B4; Leukotriene B4 - biosynthesis; Male; Medical sciences; neutrophil; Neutrophils - pathology; Rats; Rats, Sprague-Dawley; Receptors, Complement 3b - isolation & purification; Receptors, Complement 3b - therapeutic use; Reperfusion Injury - immunology; Reperfusion Injury - pathology; Reperfusion Injury - therapy; Solubility; soluble complement receptor type 1
• ISSN: 1521-6616; 1521-7035
• DOI: 10.1006/clim.1998.4635

We examined the effect of soluble complement receptor type 1 (sCR1) on mucosal injury and inflammation in a rat model of ischemia/reperfusion. Groups of vehicle- and sCR1-treated rats underwent 30 min of mesenteric ischemia followed by 60 or 120 min of reperfusion. When compared to vehicle-treated rats, treatment with sCR1 (12 mg/kg) prior to 120 min of reperfusion significantly reduced mucosal injury, neutrophil infiltration, leukotriene B4production, and restored villus height to control levels. The protective effect of sCR1 evident at 120 min of reperfusion was not observed at 60 min of reperfusion despite rapid inactivation of complement. These data suggest that complement inhibition minimized mucosal disruption by facilitating mucosal restitution or interrupting the inflammatory process. Delayed administration of sCR1 for 30 or 60 min into the reperfusion period progressively reduced the protection. sCR1-mediated rapid recovery of rat intestine after ischemia/reperfusion underscores the fundamental role of complement activation in neutrophil-mediated tissue injury.