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
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
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.
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