RESUMO
No abstract available.
Assuntos
Citocinas/farmacologia , Regulação da Expressão Gênica , Genes MHC Classe I , Antígenos de Histocompatibilidade Classe I/biossíntese , Interferons/farmacologia , Linfotoxina-alfa/farmacologia , Modelos Genéticos , Transdução de Sinais , Fator de Necrose Tumoral alfa/farmacologiaRESUMO
A soluble factor which augments the expression of major histocompatibility complex class I (MHC I) antigens on a number of murine tumor cell lines, has been isolated from the culture supernatants of mixed lymphocyte reaction of spleen cells derived from C57B1/6, Balb/c and Swiss mice. The factor, termed MHC-augmenting factor (MHC-AF) has been partially purified by Sephadex G-100 column chromatography and reverse phase HPLC. MHC-AF activity is associated with an 18 kDa molecule. MHC-AF activity was resistant to pH 2.0 treatment and partially purified MHC-AF preparations did not have any activity in L929 cell/vesicular stomatitis virus (VSV) interferon bioassay system. Antibodies to IFN-gamma did not block the activity of MHC-AF. These results indicate that a MHC-AF distinct from IFN-gamma, is produced by mouse spleen cells undergoing a mixed lymphocyte reaction.
Assuntos
Camundongos , Animais , Anticorpos/farmacologia , Quimotripsina/metabolismo , Quimotripsina/química , Estudo Comparativo , Concanavalina A/farmacologia , Temperatura Alta , Antígenos de Histocompatibilidade Classe I/metabolismo , Antígenos de Histocompatibilidade Classe I/efeitos dos fármacos , Interferon gama/farmacologia , Interferon gama/metabolismo , Interferon gama/imunologia , Linfócitos/fisiologia , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Proteínas/farmacologia , Proteínas/metabolismo , Proteínas/isolamento & purificação , Baço/citologia , Tripsina/metabolismo , Tripsina/química , Células Tumorais Cultivadas/imunologia , Células Tumorais Cultivadas/efeitos dos fármacosRESUMO
Mouse spleen cells activated in a mixed lymphocyte reaction release a soluble factor, which induces a significant proliferative response in fresh mouse spleen cells. This proliferation inducing factor (PIF) was found to be heat stable (90 degrees C for 45 min) and also resistant to trypsin or chymotrypsin treatment. By using a sizing HPLC column, the molecular weight of PIF appears to be 25 kDa. Mouse spleen cells treated with anti-thy-1 + complement lost Con-A induced proliferative responses but responded well to PIF. B cell depleted spleen cells obtained by negative selection panning, did not respond to PIF. These results indicate that B cells proliferated in response to PIF. Polymixin-B, which blocks the B cell proliferative response to LPS, did not inhibit PIF induced proliferation.
Assuntos
Camundongos , Animais , Linfócitos B/fisiologia , Linfócitos B/efeitos dos fármacos , Medula Óssea/metabolismo , Divisão Celular/fisiologia , Cromatografia Líquida de Alta Pressão , Quimotripsina/farmacologia , Relação Dose-Resposta a Droga , Substâncias de Crescimento/farmacologia , Substâncias de Crescimento/química , Temperatura Alta , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Peso Molecular , Polimixina B/farmacologia , Desnaturação Proteica , Baço/metabolismo , Timo/metabolismo , Tripsina/farmacologiaRESUMO
A novel factor which augments the expression of major histocompatibility complex I (MHC augmenting factor or MHC-AF) antigens on tumor cell lines, has been isolated from the culture supernatants of human peripheral blood mononuclear cells activated by concanavalin-A. A mouse equivalent of this factor has also been isolated from the culture supernatants of mouse spleen cells activated by mitogens or in a mixed lymphocyte reaction. Mouse MHC-AF enhances the expression of class I MHC antigens on murine tumor cell lines (EL-4 and BW5147) but not on human tumor cell lines (K562 and HR-7). Human MHC-AF on the other hand enhances the MHC I expression on both human as well as murine cell lines. Interferon gamma (IFN-gamma), a cytokine also known to enhance the expression of MHC I antigens, acts in a highly species specific manner with mouse IFN-gamma augmenting the MHC I on murine tumor cell lines and human IFN-gamma augmenting the MHC I on human tumor cell lines only. These results indicate important differences in the cross species biological activities of MHC-AF and IFN-gamma, and provide additional evidence for MHC-AF being distinct from IFN-gamma.