GAMMA-GLOBULIN, EVANS BLUE, APROTININ-A PLA(2) INHIBITOR, TETRACYCLINE AND ANTIOXIDANTS PROTECT EPITHELIAL-CELLS AGAINST DAMAGE-INDUCED BY SYNERGISM AMONG STREPTOCOCCAL HEMOLYSINS, OXIDANTS AND PROTEINASES - RELATION TO THE PREVENTION OF POSTSTREPTOCOCCAL SEQUELAE AND SEPTIC SHOCK

Citation
I. Ginsburg et M. Sadovnic, GAMMA-GLOBULIN, EVANS BLUE, APROTININ-A PLA(2) INHIBITOR, TETRACYCLINE AND ANTIOXIDANTS PROTECT EPITHELIAL-CELLS AGAINST DAMAGE-INDUCED BY SYNERGISM AMONG STREPTOCOCCAL HEMOLYSINS, OXIDANTS AND PROTEINASES - RELATION TO THE PREVENTION OF POSTSTREPTOCOCCAL SEQUELAE AND SEPTIC SHOCK, FEMS immunology and medical microbiology, 22(3), 1998, pp. 247-256
Citations number
39
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Immunology,Microbiology
ISSN journal
0928-8244
Volume
22
Issue
3
Year of publication
1998
Pages
247 - 256
Database
ISI
SICI code
0928-8244(1998)22:3<247:GEBAPI>2.0.ZU;2-W
Abstract
An in vitro model was employed to study the potential role of streptoc occal extra-cellular products, rich in streptolysin O, in cellular inj ury as related to streptococcal infections and post-streptococcal sequ elae. Extra-cellular products (EXPA) rich in streptolysin O were isola ted from type 4, group A hemolytic streptococci grown in a chemostat, in a synthetic medium. EXPA induced moderate cytopathogenic changes in monkey kidney epithelial cells and in rat heart cells pre-labeled wit h H-3-arachidonate. However very strong toxic effects were induced whe n EXP was combined with oxidants (glucose oxides generated H2O2, AAPH- induced peroxyl radical (ROO .), NO generated by sodium nitroprusside) and proteinases (plasmin, trypsin). Cell killing was distinctly syner gistic in nature. Cell damage induced by thr multi-component cocktails was strongly inhibited either by micromolar amounts of gamma globulin , and Evan's blue which neutralized SLO activity, by tetracycline, tra sylol (aprotinin), epsilon amino caproic acid and by soybean trypsin i nhibitor, all proteinase inhibitors as well as by a nonpenetrating PLA (2) inhibitor A. The results suggest that fasciitis, myositis and seps is resulting from infections with hemolytic streptococci might be caus ed by a coordinated 'cross-talk' among microbial, leukocyte and additi onal host-derived proinflammatory agents. Since attempts to prolong li ves of septic patients by the exclusive administration of single antag onists invariably failed, it is proposed that the administration of 'c ocktails' of putative inhibitors against major pro-inflammatory agoniz es generated in inflammation and infection might protect against the d eleterious effects caused by the biochemical and pharmacological casca des which are known to be activated in sepsis. (C) 1998 Federation of European Microbiological Societies. Published by Elsevier Science B.V. All rights reserved.