Abrogation of the antiproliferative activity of oncostatin M by a monoclonal antibody.
Oncostatin M (OM) is a novel cytokine which exhibits pleiotropic effects on a wide variety of normal and transformed cell lines. To determine some of the physiological functions of OM we have characterized several monoclonal antibodies to the recombinant molecule. Antibodies OM1 and OM2 bound native, but not denatured OM, suggesting they recognize non-contiguous epitopes. A third antibody, OM6, bound predominantly denatured OM. Of the two antibodies which detect discontinuous epitopes, OM2, but not OM1, was identified as a neutralizing antibody based on its ability to abrogate OM activity in the growth inhibition assay (GIA) and to inhibit OM binding in the radioreceptor assay (RRA). OM2 was equally effective in abrogating the functional effects of either natural or recombinant OM, thereby demonstrating that the active sites of these molecules are structurally similar, if not identical.
Radka
S F
SF
Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, WA 98121.
Naemura
J R
JR
Shoyab
M
M
D000818:Animals; D000911:Antibodies, Monoclonal; D016466:CHO Cells; D002455:Cell Division / Q000187:drug effects; D006224:Cricetinae; D000939:Epitopes / Q000276:immunology; D005260:Female; D007124:Immunoenzyme Techniques; D051379:Mice; D008807:Mice, Inbred BALB C / Q000276:immunology; D053683:Oncostatin M; D010455:Peptides / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000378:metabolism; D018121:Receptors, Cytokine; D053677:Receptors, Oncostatin M; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D000939:Epitopes; C508352:Osm protein, mouse; D010455:Peptides; D011956:Receptors, Cell Surface; D018121:Receptors, Cytokine; D053677:Receptors, Oncostatin M; D011994:Recombinant Proteins; D053683:Oncostatin M