The local effect of PAF on leukocyte adherence to small bowel mesenteric venules following intra-abdominal contamination

We have previously demonstrated that intra-abdominal contamination increases neutrophil infiltration into the gastrointestinal tract. The purpose of our current study was twofold: 1) to determine if leukocyte adherence to the mesenteric microvasculature occurred by local peritoneal contamination or by systemic mechanisms; and 2) to assess the role of platelet activation factor (PAF) in this process. Rats underwent cecal ligation and puncture (CLP), and 4 h after the procedure we used intravital microscopy to visualize the mesenteric microcirculation. Cecal ligation and puncture increased leukocyte adherence (22.3+/-5.5 leukocytes/100 pm) vs. sham (2.3 +/-0.9, P < 0.05). WEB-2086, a PAF receptor antagonist, prevented this increase (6.47 +/- 4.8, P < 0.05). To assess if leukocyte adherence was due to topical effects, we performed similar experiments with the small bowel exteriorized. In such cases, CLP did not increase leukocyte adherence (1.2 +/- 0.8 vs. 1.4 +/- 0.9). In addition, topical application of highly diluted fecal matter (1:11000) increased leukocyte adherence (4.8 +/- 1.2) vs. control (0.6 +/- 0.3, P < 0.05). Our study demonstrates that leukocyte adherence in the mesenteric microcirculation following intra-abdominal contamination is due to direct topical exposure to fecal matter, and it is mediated by PAF.