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Differential Roles of CD36 and αvβ5 Integrin in Photoreceptor Phagocytosis by the Retinal Pigment Epithelium

Retinal pigment epithelial (RPE) cells employ αvβ5 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...

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Autores principales: Finnemann, Silvia C., Silverstein, Roy L.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2001
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2195987/
https://www.ncbi.nlm.nih.gov/pubmed/11696594
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author Finnemann, Silvia C.
Silverstein, Roy L.
author_facet Finnemann, Silvia C.
Silverstein, Roy L.
author_sort Finnemann, Silvia C.
collection PubMed
description Retinal pigment epithelial (RPE) cells employ αvβ5 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. αvβ5 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 αvβ5 integrin.
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spelling pubmed-21959872008-04-14 Differential Roles of CD36 and αvβ5 Integrin in Photoreceptor Phagocytosis by the Retinal Pigment Epithelium Finnemann, Silvia C. Silverstein, Roy L. J Exp Med Original Article Retinal pigment epithelial (RPE) cells employ αvβ5 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. αvβ5 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 αvβ5 integrin. The Rockefeller University Press 2001-11-05 /pmc/articles/PMC2195987/ /pubmed/11696594 Text en Copyright © 2001, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Original Article
Finnemann, Silvia C.
Silverstein, Roy L.
Differential Roles of CD36 and αvβ5 Integrin in Photoreceptor Phagocytosis by the Retinal Pigment Epithelium
title Differential Roles of CD36 and αvβ5 Integrin in Photoreceptor Phagocytosis by the Retinal Pigment Epithelium
title_full Differential Roles of CD36 and αvβ5 Integrin in Photoreceptor Phagocytosis by the Retinal Pigment Epithelium
title_fullStr Differential Roles of CD36 and αvβ5 Integrin in Photoreceptor Phagocytosis by the Retinal Pigment Epithelium
title_full_unstemmed Differential Roles of CD36 and αvβ5 Integrin in Photoreceptor Phagocytosis by the Retinal Pigment Epithelium
title_short Differential Roles of CD36 and αvβ5 Integrin in Photoreceptor Phagocytosis by the Retinal Pigment Epithelium
title_sort differential roles of cd36 and αvβ5 integrin in photoreceptor phagocytosis by the retinal pigment epithelium
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2195987/
https://www.ncbi.nlm.nih.gov/pubmed/11696594
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