Differential roles of CD36 and αvβ5 integrin in photoreceptor phagocytosis by the retinal pigment epithelium

被引:117
作者
Finneman, SC
Silverstein, RL
机构
[1] Cornell Univ, Weill Med Coll, Margaret M Dyson Vis Res Inst, Dept Ophthalmol, New York, NY 10021 USA
[2] Cornell Univ, Weill Med Coll, Dept Cell Biol, New York, NY 10021 USA
[3] Cornell Univ, Weill Med Coll, Dept Med, Div Hematol & Med Oncol, New York, NY 10021 USA
关键词
phagocytosis; recognition; CD36; integrins; retinal pigment epithelium;
D O I
10.1084/jem.194.9.1289
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Retinal pigment epithelial (RPE) cells employ alphav beta5 integrin and CD36 receptors to phagocytose photoreceptor outer segment fragments (OS). We explored special properties of RPE phagocytosis to identify the contribution of CD36 to RPE phagocytosis measuring effects of CD36 antibodies on OS binding and internalization kinetics. Early, CD36 antibodies had no effect on OS binding or internalization. Both control and CD36 antibody treated RPE initiated internalization approximately 2 hours after OS challenge. Later, bivalent CD36 IgG accelerated OS engulfment while monovalent Fab fragments inhibited engulfment. Cross-linking Fab fragments restored the accelerating activity of intact IgG. Strikingly, antibodies were effective even if added to OS already bound by RPE. alphav beta5 blocking antibody reduced OS binding equally well in the presence of CD36 antibodies but CD36 antibodies accelerated internalization of remaining bound OS. Furthermore, CD36 ligation at either apical or basal RPE surface partially substituted for soluble factors that are required for internalization but not for binding of OS at the RPE apical surface. Our results demonstrate that CD36 ligation is necessary and sufficient to activate the OS internalization mechanism of RPE. They suggest that CD36 acts as a signaling molecule in postbinding steps of RPE phagocytosis independently of the OS binding receptor alphav beta5 integrin.
引用
收藏
页码:1289 / 1298
页数:10
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