Neutrophilic proteases: Mediators of formyl-methionyl-leucyl-phenylalanine-induced ileitis in rats

Journal Article · Fri Sep 01 00:00:00 EDT 1989 · Gastroenterology; (USA)

OSTI ID:5546826

von Ritter, C; Be, R; Granger, D N ^[1]

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1. 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), Journal Name: Gastroenterology; (USA) Vol. 97:3; ISSN GASTA; ISSN 0016-5085
• Country of Publication: United States
• Language: English

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59 BASIC BIOLOGICAL SCIENCES
ABSORPTION
AMINO ACIDS
ANIMAL TISSUES
ANIMALS
BETA DECAY RADIOISOTOPES
BIOLOGICAL FUNCTIONS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY
BODY FLUIDS
CARBOXYLIC ACIDS
CHELATING AGENTS
CHROMIUM 51
CHROMIUM ISOTOPES
CLEARANCE
DIGESTIVE SYSTEM
DIGESTIVE SYSTEM DISEASES
DISEASES
EDTA
ELECTRON CAPTURE RADIOISOTOPES
ENZYME INHIBITORS
ENZYMES
EVEN-ODD NUCLEI
FUNCTIONS
GASTROINTESTINAL TRACT
HYDROLASES
INTERMEDIATE MASS NUCLEI
INTESTINAL ABSORPTION
INTESTINES
ISOTOPE APPLICATIONS
ISOTOPES
LEUKOCYTES
MAMMALS
MATERIALS
MEMBRANES
MUCOUS MEMBRANES
NEUTROPHILS
NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANS
PATHOGENESIS
PEPTIDE HYDROLASES
PERFUSED TISSUES
PERMEABILITY
PHENYLALANINE
RADIOISOTOPES
RATS
RODENTS
SMALL INTESTINE
TISSUES
TRACER TECHNIQUES
UPTAKE
VERTEBRATES