The role of neutrophilic mediators in acute inflammation of the gut
Activation of granulocytes within the lamina propria by luminally derived bacterial products may represent an important mechanism in the pathogenesis of inflammatory bowel disease. One objective of this thesis was to determine the effects of luminal perfusion with N-formyl-methionyl-leucyl-phenylalanine (FMLP), a bacterial product that attracts and activates granulocytes, on mucosal permeability in different regions of the rat small intestine and colon. Mucosal permeability was measured using the blood-to-lumen clearance of {sup 51}Cr-EDTA during luminal perfusion with FMLP dissolved in Tyrode's solution. Of the bowel segments studied, mucosal permeability was significantly increased only in the distal 10 cm of the ileum. In order to define the role of neutrophilic oxidants in FMLP-induced ileitis, we evaluated the protective effect of several free radical scavengers and antioxidant enzymes. Pretreatment with the either superoxide dismutase or catalase had no effect on the FMLP-induced increase in mucosal permeability. However, treatment with either Mn-desferrioxamine, PZ51, desferrioxamine, or dimethylsulfoxide significantly attenuated FMLP-induced mucosal damage. Non-oxidative toxins released from activated neutrophil may be another mechanism by which FMLP increases mucosal permeability. In order to investigate the role of neutrophilic proteases in FMLP-induced ileitis, the effects of the nonspecific protease inhibitor soybean trypsin inhibitor, and the elastase inhibitors MeOSuc-Ala-Ala-Pro-Val-CH{sub 2}Cl(MAAPV) and Eglin C on the FMLP-induced increases in {sup 51}Cr-EDTA clearance were determined.
- Research Organization:
- Louisiana State Univ., Shreveport, LA (USA)
- OSTI ID:
- 7105251
- Resource Relation:
- Other Information: Thesis (Ph. D.)
- Country of Publication:
- United States
- Language:
- English
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DIGESTIVE SYSTEM DISEASES
PATHOGENESIS
INTESTINES
INFLAMMATION
MUCOUS MEMBRANES
PERMEABILITY
NEUTROPHILS
BIOLOGICAL FUNCTIONS
PHENYLALANINE
BIOLOGICAL EFFECTS
CATALASE
CHROMIUM 51
CLEARANCE
EDTA
ENZYME INHIBITORS
PEPTIDE HYDROLASES
PERFUSED TISSUES
RADICALS
RATS
SUPEROXIDE DISMUTASE
TOXINS
TRACER TECHNIQUES
AMINO ACIDS
ANIMAL TISSUES
ANIMALS
ANTIGENS
BETA DECAY RADIOISOTOPES
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY
BODY FLUIDS
CARBOXYLIC ACIDS
CHELATING AGENTS
CHROMIUM ISOTOPES
DIGESTIVE SYSTEM
DISEASES
ELECTRON CAPTURE RADIOISOTOPES
ENZYMES
EVEN-ODD NUCLEI
FUNCTIONS
GASTROINTESTINAL TRACT
HYDROLASES
INTERMEDIATE MASS NUCLEI
ISOTOPE APPLICATIONS
ISOTOPES
LEUKOCYTES
MAMMALS
MATERIALS
MEMBRANES
NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANS
OXIDOREDUCTASES
PATHOLOGICAL CHANGES
PEROXIDASES
RADIOISOTOPES
RODENTS
SYMPTOMS
TISSUES
TOXIC MATERIALS
VERTEBRATES
550901* - Pathology- Tracer Techniques