Role of CD18-dependent neutrophil recruitment in skin and intestinal woundhealing

CD11/CD18 is an important adhesion molecule mediating recruitment of leukoc ytes, which, in turn, may cause postoperative injury in the skin and gastro intestinal tract. The objective of the present study was to investigate the effects of inhibiting the function of CD18 on surgery-induced dermal and i ntestinal infiltration of neutrophils and on the healing of surgical skin f laps and colonic anastomosis. A flap in the dorsal skin or an end-to-end co lonic anastomosis were created in Sprague-Dawley rats. Skin necrosis and an astomotic breaking strength were analyzed 6 and 3 days after surgery, respe ctively. Tissue myeloperoxidase (MPO) was used as a marker of neutrophil re cruitment. Administration of a monoclonal antibody directed against rat CD1 8 (WT.3, 2 mg/kg) significantly decreased dermal and anastomotic MPO activi ty by more than 80%. Passive immunization against CD18 significantly improv ed flap survival, i.e. the survival was 80% in the anti-CD18 antibody group as compared to 38% in the control group. In contrast, this passive immuniz ation against CD18 had no effect on the reconstitution of the integrity of the colonic anastomosis, i.e. the anastomotic breaking strength was 1.3 +/- 0.1 and 1.3 +/- 0.3 N in the control and anti-CD18 antibody group, respect ively. These findings suggest that specific inhibition of CD18 function and reduced neutrophil recruitment may improve the survival of experimental sk in flaps and, thus, may represent a potential target for therapeutic interv ention. In contrast, we also found that blocking CD18-dependent neutrophil infiltration in the intestine had no effect on breaking strength of colonic anastomosis. Thus, neutrophils may influence the wound-healing process dif ferently in specific organs and this needs to be considered when applying a n anti-inflammatory treatment regime in order to improve tissue healing. Co pyright (C) 2001 S. Karger AG, Basel.