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Differential Roles of CD36 and vß5 Integrin in Photoreceptor Phagocytosis by the Retinal Pigment Epithelium

¹ Margaret M. Dyson Vision Research Institute, Department of Ophthalmology and Department of Cell Biology
² Division of Hematology and Medical Oncology, Department of Medicine, Weill Medical College of Cornell University, New York, NY 10021

Address correspondence to Silvia C. Finnemann, Margaret M. Dyson Vision Research Institute, Box 233 Weill Medical College of Cornell University, 1300 York Ave., New York, NY 10021. Phone: 212-746-2278; Fax: 212-746-8101; E-mail: sfinne{at}med.cornell.edu

Retinal pigment epithelial (RPE) cells employ vß5 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. vß5 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 vß5 integrin.

Key Words: phagocytosis • recognition • CD36 • integrins • retinal pigment epithelium

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