RESUMO
Considerable circumstantial evidence indicates that glycosylphosphatidylinositol (GPI) molecules of mammalian origin are able to mediate signal transduction in lymphoid cells. For example, perturbation of GPI-anchored surface proteins, but not transmembrane forms of these molecules, can lead to the activation of T lymphocytes. GPIs appear also to be precursors of pharmacologically active phosphoinositol-glycans which mediate responses to hormones such as insulin, nerve growth factor and IL-2. Nonetheless, the biochemical mechanisms of signal transduction by GPIs remain obscure. We have shown that structurally defined GPIs of protozoal parasite origin are able to mediate signal transduction in host macrophages and lymphocytes, by substituting for the putative endogenous GPI-based signalling mechanisms of the host. Signalling by parasite GPIs appears to involve the activation of protein tyrosine kinase and protein kinase C. Evidence from other sources indicates that structurally variant GPIs may provide anergic signals to down-regulate host cell function. These phenomena may represent mechanisms by which eukaryotic parasites regulate host cell function, and can explain a variety of pathological and immunological features of protozoal infections. Furthermore, protozoal GPIs may prove to be an informative model system for the analysis of GPI-mediated signal transduction in lymphocytes and macrophages.
Assuntos
Eucariotos/química , Glicosilfosfatidilinositóis/fisiologia , Proteína Quinase C/metabolismo , Transdução de Sinais , Animais , Citocinas/fisiologia , Eucariotos/fisiologia , Glicosilfosfatidilinositóis/química , Ativação Linfocitária , Linfócitos/fisiologia , Ativação de Macrófagos , Macrófagos/fisiologia , Plasmodium falciparum/química , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Considerable circumstantial evidence indicates that glycosylphosphatidylinositol (GPI) molecules of mammalian origin are able to mediate signal transduction in lymphoid cells. For example, pertubation of GPI-anchored surface proteins, but not transmembrane forms of these molecules, can lead to the activation of T lymphocytes. GPIs appear also to be precursors of pharmacologically active phosphoinositol-glycans which mediate responses to hormones such as insulin, nerve growth factor and IL-2. Nonetheless, the biochemical mechanisms of signal transduction by GPIs remain obscure. We have shown that structurally defined GPIs of protozoal parasite origin are able to mediate signal transduction in host macrophages and lymphocytes, by substituting for the putative endogenous GPI-based signalling mechanisms of the host. Signalling by parasite GPIs appears to involve the activation of protein tyrosine kinase and protein C. Evidence from other sources indicates that structurally variant GPIs may provide anergic signals to down-regulate host cell function. These phenomena may represent mechanisms by which eukaryotic parasites regulate host cell function, and can explain a variety of pathological and immunological features of protozoal infections. Furthermore, protozoal GPIs may prove to be an informative model system for the analysis of GPI-mediated signal transduction in lymphocytes and macrophages
Assuntos
Citocinas , Eucariotos , Fosfatidilinositóis/metabolismo , Glicolipídeos/metabolismo , Leishmania , Malária Falciparum , Transdução de Sinais , Linfócitos B , Fosfatidilinositóis/química , Glicolipídeos/química , Macrófagos , Plasmodium falciparumRESUMO
Four monoclonal antibodies produced against Plasmodium falciparum recognize an antigen in merozoites that is localized in rhoptries, as judged by a punctate, double dot fluorescence pattern. All four antibodies bound to the same affinity purified antigen in a two site immunoradiometric assay. Immunoprecipitation of antigen by monoclonal antibody followed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis yielded protein bands of 80, 66 and 42 kDa. Western blotting gave bands of 80 and 66 kDa only with three of the antibodies: the fourth did not blot. Based on protease inhibitor data the 66 kDa band is considered to be a cleavage product of the 80 kDa band, but the 42 kDa band does not appear to derive from the latter and may be a coprecipitation product. This group of antigens labels with both [35S]methionine and [3H]histidine. Two of the monoclonal antibodies inhibited merozoite invasion of erythrocytes. One of these inhibitors recognizes a variable epitope, whereas the second recognizes a highly conserved epitope present in all 106 primary isolates of P. falciparum tested from Brazil, Thailand and Papua New Guinea.
Assuntos
Antígenos de Protozoários/imunologia , Epitopos/imunologia , Eritrócitos/parasitologia , Plasmodium falciparum/imunologia , Animais , Anticorpos Monoclonais/imunologia , Antígenos de Protozoários/análise , Brasil , Eletroforese em Gel de Poliacrilamida , Epitopos/análise , Eritrócitos/imunologia , Imunofluorescência , Humanos , Técnicas de Imunoadsorção , Malária/imunologia , Malária/parasitologia , Organoides/imunologia , Papua Nova Guiné , Plasmodium falciparum/crescimento & desenvolvimento , Plasmodium falciparum/ultraestrutura , Radioimunoensaio , TailândiaRESUMO
The expression by Plasmodium falciparum of a specific S-antigen has been examined in primary isolates in different regions of the world using a monoclonal antibody that recognizes an epitope within a known repeated amino acid sequence. The epitope was expressed by a small proportion of primary isolates in each of Brazil, Thailand and Papua New Guinea, demonstrating that this S-antigen gene is widespread. The data are consistent with the possibility that the occurrence of P. falciparum strains expressing a particular S-antigen is periodic, related to the duration of immunity against that antigen in a given human population.