Open AccessGamma globulin, Evan's 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 post‐streptococcal sequelae and septic shock 1
Author(s) -
Ginsburg Isaac,
Sadovnic Milu
Publication year - 1998
Publication title -
fems immunology & medical microbiology
Language(s) - English
Resource type - Journals
eISSN - 1574-695X
pISSN - 0928-8244
DOI - 10.1111/j.1574-695x.1998.tb01213.x
Subject(s) - microbiology and biotechnology , aprotinin , biology , streptolysin , bordetella pertussis , hemolysin , trypsin inhibitor , biochemistry , trypsin , enzyme , bacteria , medicine , virulence , genetics , surgery , bacterial protein , gene
An in vitro model was employed to study the potential role of streptococcal extra‐cellular products, rich in streptolysin O, in cellular injury as related to streptococcal infections and post‐streptococcal sequelae. Extra‐cellular products (EXPA) rich in streptolysin O were isolated 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 with 3 H‐arachidonate. However very strong toxic effects were induced when EXP was combined with oxidants (glucose oxides generated H 2 O 2 , AAPH‐induced peroxyl radical (ROO⋅), NO generated by sodium nitroprusside) and proteinases (plasmin, trypsin). Cell killing was distinctly synergistic in nature. Cell damage induced by the multi‐component cocktails was strongly inhibited either by micromolar amounts of gamma globulin, and Evan's blue which neutralized SLO activity, by tetracycline, trasylol (aprotinin), epsilon amino caproic acid and by soybean trypsin inhibitor, all proteinase inhibitors as well as by a non‐penetrating PLA 2 inhibitor A. The results suggest that fasciitis, myositis and sepsis resulting from infections with hemolytic streptococci might be caused by a coordinated ‘cross‐talk’ among microbial, leukocyte and additional host‐derived pro‐inflammatory agents. Since attempts to prolong lives of septic patients by the exclusive administration of single antagonists invariably failed, it is proposed that the administration of ‘cocktails’ of putative inhibitors against major pro‐inflammatory agonizes generated in inflammation and infection might protect against the deleterious effects caused by the biochemical and pharmacological cascades which are known to be activated in sepsis.