Dissociation between murine spleen cell mitogenic activity of enterotoxin contaminants and anti-tumor activity of staphylococcal protein A.
Soluble staphylococcal protein A (SpA) in the form of high m.w. complexes with IgG has been shown to significantly inhibit the growth of Meth A fibrosarcomas in BALB/c mice. Although SpA reportedly is a potent T cell mitogen that can induce immune cell proliferation and production of humoral factors with anti-tumor activity, it has been suggested that mitogenic enterotoxin contaminants might be responsible for these effects. The purpose of the present study was to investigate the nature of SpA-induced cell proliferation and the relationship between mitogenicity and the anti-tumor effect that we observed in our mouse model. SpA stimulated the proliferation of a mixed population of splenic B and T cells from BALB/c mice, but activity did not require the presence of IgG in the culture medium. Furthermore, mitogenic activity could be inhibited completely by anti-SEA plus anti-SEB, but was unaffected by anti-SpA. HPLC-purified SpA was inactive while the mitogenic factor(s) had the same retention time as authentic enterotoxin and its activity was inhibited by anti-SEA and anti-SEB, but not by anti-SpA. Enterotoxin-free rSpA produced in Escherichia coli had the same IgG binding capacity as the staphylococcal product but was not mitogenic. These data indicate that SEA and SEB completely account for mitogenicity in SpA preparations. In contrast, we found that optimal concentrations of rSpA as well as crude and HPLC purified staphylococcal SpA were equally effective in inhibiting the growth of established Meth A fibrosarcomas demonstrating that SpA is responsible for antitumor activity without any apparent role for enterotoxins.
Das
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Department of Biochemistry, Baylor College of Medicine, Houston, TX 77030.
Langone
J J
JJ
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D004768:Enterotoxins / Q000302:isolation & purification / Q000494:pharmacology*; D005260:Female; D005354:Fibrosarcoma / Q000188:drug therapy; D007074:Immunoglobulin G / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008934:Mitogens / Q000494:pharmacology*; D013205:Staphylococcal Protein A / Q000302:isolation & purification / Q000494:pharmacology*
D000970:Antineoplastic Agents; D004768:Enterotoxins; D007074:Immunoglobulin G; D008934:Mitogens; D013205:Staphylococcal Protein A; C026066:enterotoxin A, Staphylococcal; C031818:enterotoxin B, staphylococcal