Structure-function studies for in vitro chemical inhibition of Fc gamma receptor-mediated phagocytosis.

Foo, A; Fletcher, S; Langler, R; Porter, C; Branch, DR

Journal article

Structure-function studies for in vitro chemical inhibition of Fc gamma receptor-mediated phagocytosis.

Abstract:: BACKGROUND: Previous studies [Transfusion 2005;45:384] showed that certain chemical compounds containing sulfur-reactive groups can inhibit Fcgamma receptor (FcgammaR)-mediated phagocytosis in vitro. These studies, however, did not prove that only sulfur functionality-induced reactivity was efficacious. In an effort to develop a drug-based approach for the future treatment of immune-mediated cytopenias, these earlier findings have now been extended and this chemically induced interference with FcgammaR-mediated phagocytosis of anti-D-coated red cells (RBCs) was examined to assess the optimal structural requirements for the inhibitory effect. STUDY DESIGN AND METHODS: Chemical compounds were purchased or synthesized and used for the assessment of which chemical moiety(-ies) were required for successful inhibition of in vitro phagocytosis of anti-D-coated RBCs with a monocyte monolayer assay. RESULTS: Using compounds having similar structures but differences in reactive moieties, it was proved that the only chemical moiety that was required for inhibition of FcgammaR-mediated phagocytosis in vitro was a disulfide bond. It is also shown, however, that a p-nitrophenyl group provides significant enhancement to the inhibitory effect of disulfide-containing compounds. Involvement of carbonyl and hydroxyl functional groups was also able to be ruled out. CONCLUSION: Our results confirm and extend previous studies that suggested that only those compounds that target free sulfhydryl groups on the monocyte-macrophage are most effective at blocking phagocytosis of antibody-coated RBCs in vitro. It is also shown that p-nitrophenyl substituent groups have an enhancing effect on the efficacy of disulfide bond-containing compounds. These findings should aid in the design of a drug-based approach for the future treatment of immune cytopenias.

Publication status:: Published

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APA Style

Foo, A., Fletcher, S., Langler, R., Porter, C., & Branch, D. R. (2007). Structure-function studies for in vitro chemical inhibition of Fc gamma receptor-mediated phagocytosis. Transfusion, 47(2), 290–298.

MLA Style

Foo, A, et al. “Structure-Function Studies for in Vitro Chemical Inhibition of Fc Gamma Receptor-Mediated Phagocytosis.” Transfusion, vol. 47, no. 2, 2007, pp. 290–98.

Chicago Style

Foo, A, S Fletcher, R Langler, C Porter, and DR Branch. 2007. “Structure-Function Studies for in Vitro Chemical Inhibition of Fc Gamma Receptor-Mediated Phagocytosis.” Transfusion 47 (2): 290–98.
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