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dc.contributor.authorSCHNECK, JONATHAN PHILIP
dc.identifier.citationSource: Dissertation Abstracts International, Volume: 44-07, Section: B, page: 2073.
dc.description.abstractVariants with altered Fc-receptor mediated phagocytosis, some of which were corrected by the addition of 8 Br-cAMP, were isolated from the macrophage-like cell line J774.2. Monoclonal mouse IgG2a and IgG2b were used to determine the Fc-receptor specificity of the defects. Most variants analyzed were defective in IgG2a-mediated phagocytosis. One variant had a general Fc-mediated phagocytosis defect. Variants selected in the presence of 8 Br-cAMP had different characteristics; one was unresponsive to stimulation of IgG2a- and IgG2b-mediated phagocytosis; two showed selective defects in sensitivity of IgG2a-mediated phagocytosis to cAMP; one was completely responsive to stimulation of phagocytosis by cAMP.;A monomeric ('125)I IgG2a binding assay was used to assess Fc-receptor expression. One variant was deficient in the binding of ('125)I IgG2a. Scatchard analysis of the binding data showed that this variant expressed fewer then half the high affinity receptors of the parental line, but the affinity of the receptors for monomeric IgG2a remained unchanged (Ka(TURN)6 x 10('6) M('-1)). Another of the nonphagocytic variants had no apparent defect in its Fc-receptors. Upon exposure to cAMP all lines analyzed, even a variant cell line whose phagocytosis was not corrected by cAMP, showed an increase in Fc-receptor expression.;The role of plasminogen activator as endogenous inhibitor of phagocytosis was analyzed. Nitrophenyl-guanidinobenzoate, a serine protease inhibitor with a high degree of specificity for plasminogen activator, augmented Fc-mediated phagocytosis. Urokinase, a purified plasminogen activator, markedly decreased Fc-mediated phagocytosis. No effect of exogenous plasminogen activator was seen on Fc-receptor expression. The results indicate that (a) distinct classes of variants in the phagocytosis pathway can be isolated; (b) IgG2a and IgG2b phagocytosis are separable at a point distal to Fc-receptor binding; (c) there are steps subsequent to Fc-receptor binding that are limiting for phagocytosis and sensitive to cAMP; (d) cAMP affects Fc-receptor expression; and (e) plasminogen activator may be an endogenous inhibitor of Fc-receptor mediated phagocytosis.;Having analyzed variants selected from J774.2 which were defective in phagocytosis or cAMP metabolism, I investigated the role of cAMP in mediating the effects of interferon on Fc-receptor mediated phagocytosis, intracellular cAMP levels, antiviral activity, growth inhibition, and inhibition of thymidine incorporation. . . . (Author's abstract exceeds stipulated maximum length. Discontinued here with permission of author.) UMI.
dc.publisherProQuest Dissertations & Theses

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