This proposal is directed toward an understanding of the cellular and molecular mechanisms that control transport of IgG across the endothelial layer of the human placenta. Transport of mother's protective antibodies to the developing individual is vital to survival and is basic to maternal-fetal biology. Understanding this process is important for the health and well being of the fetus and newborn and will also have impact on a variety of disease states that devolve from IgG transport to the fetus. Additionally, understanding the IgG transport mechanism offers the potential for manipulation of the process for therapeutic purposes. Our basic hypothesis holds that IgG transport across the endothelium is an active process controlled by one of the known receptors for IgG, namely Fc-gamma-RIIb, and the specialized plasma membrane microdomains known as caveolae. The precise cellular and molecular details of this process are unknown. The experiments laid out in this proposal are designed to test our hypothesis and uncover the cellular and molecular mechanisms that permit transport of protective antibodies from mother to fetus.
The specific aims of this proposal are to determine: (l) the potential for Fc-gammaRIIb to act as an IgG transporter and (2) the role that caveolae play in IgG transport. Our approaches to testing the predictions of this hypothesis incorporate methods of cell biology, immunology, biochemistry, ultrastructural analysis, and molecular biology.
| Mohanty, Sudhasri; Kim, Jonghan; Ganesan, Latha P et al. (2013) Abundant intracellular IgG in enterocytes and endoderm lacking FcRn. PLoS One 8:e70863 |
| Ganesan, Latha P; Kim, Jonghan; Wu, Yun et al. (2012) Fc?RIIb on liver sinusoidal endothelium clears small immune complexes. J Immunol 189:4981-8 |
| Ganesan, Latha P; Mohanty, Sudhasri; Kim, Jonghan et al. (2011) Rapid and efficient clearance of blood-borne virus by liver sinusoidal endothelium. PLoS Pathog 7:e1002281 |
| Mohanty, Sudhasri; Kim, Jonghan; Ganesan, Latha P et al. (2010) IgG is transported across the mouse yolk sac independently of FcgammaRIIb. J Reprod Immunol 84:133-44 |
| Mohanty, S; Anderson, C L; Robinson, J M (2010) The expression of caveolin-1 and the distribution of caveolae in the murine placenta and yolk sac: parallels to the human placenta. Placenta 31:144-50 |
| Robinson, John M; Ackerman 4th, William E; Tewari, Arun K et al. (2009) Isolation of highly enriched apical plasma membranes of the placental syncytiotrophoblast. Anal Biochem 387:87-94 |
| Robinson, J M; Vandré, D D; Ackerman 4th, W E (2009) Placental proteomics: a shortcut to biological insight. Placenta 30 Suppl A:S83-9 |
| Kim, Jonghan; Mohanty, Sudhasri; Ganesan, Latha P et al. (2009) FcRn in the yolk sac endoderm of mouse is required for IgG transport to fetus. J Immunol 182:2583-9 |
| Kim, Jonghan; Bronson, C L; Wani, Manzoor A et al. (2008) Beta 2-microglobulin deficient mice catabolize IgG more rapidly than FcRn- alpha-chain deficient mice. Exp Biol Med (Maywood) 233:603-9 |
| Robinson, J M; Ackerman 4th, W E; Kniss, D A et al. (2008) Proteomics of the human placenta: promises and realities. Placenta 29:135-43 |
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