Correlation of oncostatin M secretion by human retrovirus-infected cells with potent growth stimulation of cultured spindle cells from AIDS-Kaposi's sarcoma.
Oncostatin M (OM), a 30-kDa glycoprotein, recently was identified as a major growth-promoting factor in the conditioned medium (CM) of the 38-0 cell line, a CD4,+ chronically human T lymphotropic virus type (HTLV)-II-infected, transformed T cell line. CM 38-0 induced the proliferation of spindle cells cultured in vitro from AIDS-associated Kaposi's sarcoma (AIDS-KS) cells. To determine how much of the AIDS-KS cell growth activity present in 38-0 CM was because of the presence of OM, we depleted OM by using specific mAb-affinity chromatography. OM purified from this CM stimulated AIDS-KS cell growth in a concentration-dependent fashion. The effluent, completely depleted of OM, failed to induce growth of AIDS-KS cells. To detect the constitutive release of OM by cells acutely or chronically infected with either HTLV-I, HTLV-II, or HIV-1, we utilized an enzyme-linked immunoassay. Whereas the chronically infected cells released significant levels of OM, the acutely infected cells released little or no OM. The presence of OM in HIV-1-infected T-cell CM correlated completely with AIDS-KS cell growth activity. Infrequently, low level AIDS-KS cell growth activity was seen in the absence of OM. This correlated with relatively high levels of IL-6 in the CM. In a CM-containing OM in the absence of detectable IL-6, a neutralizing antibody to OM completely abrogated KS cell growth activity. The presence of specific oncostatin M receptors on the KS cell lines was confirmed by cross-linking experiments. The results shown here suggest that T cells chronically infected with HIV-1 can secrete OM, which may play a role in the initiation or progression of AIDS-KS lesions, either alone, or in concert with IL-6.
Radka
S F
SF
Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, WA 98121.
Nakamura
S
S
Sakurada
S
S
Salahuddin
S Z
SZ
D000163:Acquired Immunodeficiency Syndrome / Q000378:metabolism* / Q000473:pathology*; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002846:Chromatography, Affinity; D003432:Cross-Linking Reagents; D017077:Culture Media, Conditioned; D006800:Deltaretrovirus Infections / Q000378:metabolism*; D006133:Growth Substances / Q000378:metabolism*; D015658:HIV Infections / Q000378:metabolism*; D006801:Humans; D015850:Interleukin-6 / Q000032:analysis; D053683:Oncostatin M; D010455:Peptides / Q000032:analysis / Q000276:immunology / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000737:chemistry; D012514:Sarcoma, Kaposi / Q000378:metabolism* / Q000473:pathology
D000911:Antibodies, Monoclonal; D003432:Cross-Linking Reagents; D017077:Culture Media, Conditioned; D006133:Growth Substances; D015850:Interleukin-6; C508351:OSM protein, human; D010455:Peptides; D011956:Receptors, Cell Surface; D053683:Oncostatin M