Neutrophilic proteases: Mediators of formyl-methionyl-leucyl-phenylalanine-induced ileitis in rats
- Louisiana State Univ. Medical Center, Shreveport (USA)
N-formyl-methionyl-leucyl-phenylalanine (FMLP), a tripeptide of bacterial origin that activates and attracts neutrophils, increases mucosal permeability when placed in the lumen of rat ileum. Although studies using neutropenic animals demonstrate the essential role of neutrophils in FMLP-induced mucosal injury, the neutrophil-derived chemical mediator of this injury process remains undefined. The objective of this study was to determine whether neutrophilic proteases mediate FMLP-induced increases in mucosal permeability. The blood-to-lumen clearance of {sup 51}Cr-ethylenediaminetetraacetate was used to monitor mucosal permeability in the terminal ileum of Sprague-Dawley rats. In control (untreated) animals luminal perfusion with 10(-5) M FMLP resulted in twofold and fourfold increases in {sup 51}Cr-ethylenediaminetetraacetate clearance after 1 and 2 h of FMLP exposure, respectively. Pretreatment with the nonspecific serine protease inhibitor, soybean trypsin inhibitor (15 mg/kg), significantly attenuated the clearance responses normally observed during luminal perfusion with FMLP. The specific elastase inhibitors MeOSuc-Ala-Ala-Pro-Val-CH{sub 2}Cl (10 mg/kg) and Eglin c (8 mg/kg) significantly attenuated the FMLP-induced increases in ethylenediaminetetraacetate clearance observed after both 1 and 2 h of exposure. The results of this study indicate that neutrophilic proteases mediate at least part of the increased mucosal permeability induced by luminal exposure to FMLP.
- OSTI ID:
- 5546826
- Journal Information:
- Gastroenterology; (USA), Vol. 97:3; ISSN 0016-5085
- Country of Publication:
- United States
- Language:
- English
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