Systémová enzymoterapie pro odborníky

Modulation of growth factor binding properties of a2-macroglobulin by enzyme therapy

Lauer D., Müller R., Cott C., Otto A., Naumann M., Birkenmeier G.

Institute of Biochemistry, University of Leipzig, Leipzig, Germany

Cancer Chemother Pharmacol (2001) 47: 4 - 9.

Abstract

Purpose: To investigate the binding of transforming growth factor-beta (TGF-b) to human a2-macroglobulin upon oral treatment of patients with proteases.
Methods: Volunteers were given a cocktail of active proteinases (Phlogenzym) composed of trypsin, bromelain and the additive rutoside orally over a period of 7 days at low dose followed by a bolus application. Before and after medication plasma was immediately withdrawn and binding of ¹²⁵I-TGF-b to the proteinase inhibitor a2-macroglobulin was determined by electrophoresis and g-counting. Cell culture experiments were performed to study the effect of transformed a2-macroglobulin on TGF-b-stimulated proliferation of skin fibroblasts.
Results: Ingestion of proteinases was found to trigger the formation of intermediate forms of a2-macroglobulin displaying high affinity to TGF-b. Maximum binding of TGF-b was observed 1-2 h after bolus ingestion, and steadily levelled off with time. In vitro experiments demonstrated that complex formation of diverse proteinases (trypsin, a-chymotrypsin, bromelain and plasmin) with a2-macroglobulin conferred binding of ¹²⁵I-TGF-b. a2-Macroglobulin transformed by methyl-amine or proteinases was found to abolish the TGF-b effect on fibroblasts in cell culture.
Conclusions: Intestinal absorption of proteinases triggers the formation of TGF-b binding species of a2-macroglobulin in blood. Mediated by this process high concentrations of TGF-b might be reduced via enhanced clearance of a2-macroglobulin-TGF-b complexes. Thus, proteinase therapy may have beneficial effects in treatment of fibrosis and certain cancers accompanied by excessively high TGF-b concentrations.
Key words: Proteinase therapy • TGF-b • a2-macroglobulin • Cancer • Fibrosis


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Zánět a jeho ovlivnění SET Zvýšení využitelnosti antibiotik proteolytickými enzymy Angiologie, flebologie Gynekologie Chirurgie, traumatologie, ortopedie Imunologie Lymfologie ORL Pediatrie Revmatologie Sportovní medicína Stomatologie Urologie Literatura Časopisy s Impact faktorem Ostatní literatura SPC Wobenzym SPC Phlogenzym	Modulation of growth factor binding properties of a2-macroglobulin by enzyme therapy Lauer D., Müller R., Cott C., Otto A., Naumann M., Birkenmeier G. Institute of Biochemistry, University of Leipzig, Leipzig, Germany Cancer Chemother Pharmacol (2001) 47: 4 - 9. Abstract Purpose: To investigate the binding of transforming growth factor-beta (TGF-b) to human a2-macroglobulin upon oral treatment of patients with proteases. Methods: Volunteers were given a cocktail of active proteinases (Phlogenzym) composed of trypsin, bromelain and the additive rutoside orally over a period of 7 days at low dose followed by a bolus application. Before and after medication plasma was immediately withdrawn and binding of ¹²⁵I-TGF-b to the proteinase inhibitor a2-macroglobulin was determined by electrophoresis and g-counting. Cell culture experiments were performed to study the effect of transformed a2-macroglobulin on TGF-b-stimulated proliferation of skin fibroblasts. Results: Ingestion of proteinases was found to trigger the formation of intermediate forms of a2-macroglobulin displaying high affinity to TGF-b. Maximum binding of TGF-b was observed 1-2 h after bolus ingestion, and steadily levelled off with time. In vitro experiments demonstrated that complex formation of diverse proteinases (trypsin, a-chymotrypsin, bromelain and plasmin) with a2-macroglobulin conferred binding of ¹²⁵I-TGF-b. a2-Macroglobulin transformed by methyl-amine or proteinases was found to abolish the TGF-b effect on fibroblasts in cell culture. Conclusions: Intestinal absorption of proteinases triggers the formation of TGF-b binding species of a2-macroglobulin in blood. Mediated by this process high concentrations of TGF-b might be reduced via enhanced clearance of a2-macroglobulin-TGF-b complexes. Thus, proteinase therapy may have beneficial effects in treatment of fibrosis and certain cancers accompanied by excessively high TGF-b concentrations. Key words: Proteinase therapy • TGF-b • a2-macroglobulin • Cancer • Fibrosis
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