alpha-chymotrypsin and Granuloma

We investigated the angiogenic effect of chymase, an alternative angiotensin II-generating enzyme, on angiogenesis using hamster sponge implant model. Exogenous administration of angiotensin II (Ang II) or angiotensin I (Ang I) directly into the sponges enhanced angiogenesis, as determined from the hemoglobin contents in the sponge granuloma tissues. Chymostatin, an inhibitor of chymase, inhibited angiogenesis induced by Ang I but not by Ang II, suggesting the presence of a chymase-like Ang II-generating activity in the sponge granuloma. TCV-116 (5 mg/kg p.o.), an antagonist of Ang II type 1 receptor, and chymostatin suppressed bFGF-induced angiogenesis, suggesting the significance of the endogenous angiotensin system. Chymase activity in the sponge granuloma increased in parallel with the rise in hemoglobin contents induced by bFGF. We also examined the effects of direct administration of human pro-chymase gene or purified hamster chymase, and demonstrated that in vivo human pro-chymase gene transfection and direct injection of purified chymase enhanced angiogenesis, which was 50% inhibited by TCV-116. Sponge granulomas treated with Ang II was supressed by vascular endothelial growth factor (VEGF) antisense. Our results suggest that chymase enhanced angiogenesis partly through the local production of Ang II, followed by up-regulation of VEGF.

Topics: Angiotensin I; Angiotensin II; Angiotensin Receptor Antagonists; Animals; Benzimidazoles; Biphenyl Compounds; Chymases; Chymotrypsin; Cricetinae; Endothelial Growth Factors; Granuloma; Hemoglobins; Humans; Lymphokines; Male; Mesocricetus; Neovascularization, Physiologic; Oligopeptides; Protein Isoforms; Serine Endopeptidases; Serine Proteinase Inhibitors; Tetrazoles; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors

Serine proteinases have the potential to influence the degradation of connective tissue in chronic periodontitis, which may progress episodically at individual tooth sites. Elastase-, chymotrypsin- and tryptase-like proteinase activity in homogenized gingival tissue were measured using, respectively, the selective peptide substrates MeOSuc-Ala-Ala-Pro-Val-AFC. MeOSuc-Phe-Pro-Phe-AFC and Z-Ala-Arg-Arg-AFC. Each tooth site was assayed separately and divided, where appropriate, into gingival tissue and granulomata. Elastase-like activity was detected in only about half of the sites and with large variations. Chymotrypsin-like activity decreased with increasing pocket depth, clinical attachment level, gingival index and gingival bleeding index. Tryptase-like activity did not vary consistently with clinical measures. Chymotrypsin- and tryptase-like proteinase activity were much higher in gingival tissue than in granulomata. These effects are best explained by the likely influence (or lack of influence) of the endogenous serum and tissue inhibitors of serine proteinases, the different cellular origins of the enzymes, and their relative affinities for their substrates.

Topics: Adult; Chronic Disease; Chymotrypsin; Female; Gingiva; Gingival Pocket; Gingivitis; Granuloma; Humans; Male; Middle Aged; Pancreatic Elastase; Peptide Hydrolases; Periodontal Index; Periodontitis; Serine Endopeptidases

The effect of trypsin or chemotrypsin on the levels of benzylpenicillin, ampicillin, oxacillin, kanamycin or tetracycline in the peritoneal inflammation fluid, as well as the effect of trypsin on penetration of these antibiotics into the granulemas of 2 types was studied. It was found that intramuscular administration of the enzymes to animals in a dose of 10 mg/kg resulted in increased levels of penicillins and kanamycin in the inflammation peritoneal fluid. An analogous effect of trypsin was observed with respect to experimental granulemas. The levels of tetracycline in restricted inflammatory foci increased only after intraperitoneal administration of trypsin to rats. Increased penetration of benzylpenicillin into the peritoneal fluid and connective tissue granulema under the effect of the enzymes was observed. The effect of trypsin on penetration of benzylpenicillin into granulema according to Selie did not differ from the effect of the enzyme on penetration of semisynthetic penicillins and kanamycin into it.

Topics: Animals; Anti-Bacterial Agents; Ascitic Fluid; Biopharmaceutics; Blood; Chymotrypsin; Drug Interactions; Granuloma; Inflammation; Injections, Intramuscular; Peptide Hydrolases; Rats; Trypsin

Topics: Ampicillin; Bacillus; Chymotrypsin; Dose-Response Relationship, Drug; Drug Interactions; Granuloma; Injections, Intramuscular; Kidney; Kinetics; Liver; Lung; Microbial Sensitivity Tests; Penicillin G; Penicillins; Time Factors; Trypsin

Topics: Animals; Chymotrypsin; Drug Interactions; Endopeptidases; Granuloma; Injections, Intramuscular; Injections, Intraperitoneal; Kinetics; Peptide Hydrolases; Rats; Tetracycline; Time Factors

Topics: Animals; Brain; Chymotrypsin; Drug Therapy, Combination; Granuloma; Kanamycin; Kidney; Liver; Lung; Myocardium; Rats; Spleen

Topics: Animals; Chymotrypsin; Cortisone; Drug Synergism; Granuloma; Hyaluronoglucosaminidase; Inflammation; Penicillin G; Penicillin G Procaine; Rats

Topics: Adrenalectomy; Animals; Anti-Inflammatory Agents; Aspirin; Bromelains; Carrageenan; Chymotrypsin; Edema; Enzyme Activation; Female; Flufenamic Acid; Granuloma; Guinea Pigs; Histamine Release; Hot Temperature; Hydrocortisone; Immune Sera; Indomethacin; Injections, Intramuscular; Kaolin; Male; Peptide Hydrolases; Phenylbutazone; Rats; Serotonin; Serratia; Time Factors

Topics: Animals; Chymotrypsin; Drug Synergism; Exudates and Transudates; Granuloma; Inflammation; Penicillin G; Rats; Staphylococcus; Stimulation, Chemical; Turpentine

Topics: Adrenalectomy; Animals; Bradykinin; Chymotrypsin; Deoxyribonucleases; Edema; Fibrinolysin; Granuloma; Inflammation; Male; Muramidase; Pancreatin; Peptide Hydrolases; Rats; Serratia; Trypsin

Topics: Adolescent; Cholesterol; Chymotrypsin; Deafness; Female; Granuloma; Hematoma; Humans; Otitis Media; Suppuration; Tympanic Membrane

Topics: Aminocaproates; Animals; Aspergillus; Bromelains; Carbon Tetrachloride Poisoning; Chymotrypsin; Granuloma; Papain; Peptide Hydrolases; Plasminogen; Rats; Streptokinase; Trypsin

Topics: Animals; Chymotrypsin; Exercise; Granuloma; Hematologic Tests; Inflammation

Topics: Chymotrypsin; Endopeptidases; Granuloma; Hydrolases; Inflammation; Peptide Hydrolases; Trypsin