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 microm) 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 (1:1000) 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.
Smalley
D M
DM
Department of Surgery, University of Kansas Medical Center, Kansas City 66160, USA.
Childs
E W
EW
Cheung
L Y
LY
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects*; D005243:Feces; D007416:Intestinal Perforation / Q000150:complications; D007421:Intestine, Small / Q000098:blood supply*; D007962:Leukocytes / Q000187:drug effects*; D008297:Male; D008642:Mesenteric Veins / Q000187:drug effects*; D008833:Microcirculation; D009102:Multiple Organ Failure / Q000209:etiology; D020556:Neutrophil Infiltration / Q000187:drug effects*; D010538:Peritonitis / Q000209:etiology / Q000473:pathology*; D010972:Platelet Activating Factor / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014699:Venules
D010972:Platelet Activating Factor