Ileal mucosal response to bacterial toxin challenge.
BACKGROUND
The cause of postinjury intestinal mucosal barrier disruption remains obscure. The present study examines the hypothesis that the bacterial toxin formyl-methionyl leucyl phenylalanine (FMLP) plays an initial role in this process.


METHODS
Mucosal permeability to fluorescein isothiocyanate-labeled dextran (4,400 molecular weight) was measured in perfused distal rat ileum with and without FMLP. Dextran and myeloperoxidase appearance in the lumenal perfusate was assessed in response to surrogates of traumatic stress: ischemia/reperfusion, total abdominal irradiation, and total parenteral nutrition. Recovery of FMLP in the effluent of static closed and perfused ileal loops was determined by mass spectrometry. Release of mast cell mediators in the presence of FMLP was determined in ileal everted sacs.


RESULTS
Seventy-five percent of FMLP was recovered in perfusion effluent in contrast to 5% in closed loops. There was a transient increase in ileal permeability in FMLP/perfused, untreated rats, and in ischemia/reperfusion and total parenteral nutrition treated rats that was recorded with a concomitant increment in myeloperoxidase (inflammatory marker) in all experimental models except irradiated rats, which were unresponsive to FMLP. FMLP responsiveness was associ. ated with a significant rise in release of serotonin (mast cell mediator).


CONCLUSIONS
These results suggest that mast cells and other resident inflammatory cells within the gut wall are involved in FMLP-induced changes in mucosal barrier permeability and raise the possibility that under conditions of traumatic stress, proinflammatory mediators within the gut wall might be activated by toxic factors in the gut lumen.
Harari
Y
Y
Department of Surgery, University of Texas-Houston Health Science Center, 77225, USA.
Weisbrodt
N W
NW
Moody
F G
FG
D000818:Animals; D001427:Bacterial Toxins / Q000493:pharmacokinetics / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D003911:Dextrans / Q000493:pharmacokinetics; D007082:Ileum / Q000187:drug effects* / Q000378:metabolism; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D013058:Mass Spectrometry; D009102:Multiple Organ Failure / Q000503:physiopathology*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000493:pharmacokinetics / Q000494:pharmacology*; D010539:Permeability; D009195:Peroxidase / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley
D001427:Bacterial Toxins; D003911:Dextrans; D009240:N-Formylmethionine Leucyl-Phenylalanine; D009195:Peroxidase