Integrin alphavbeta5 is not required for the phagocytosis of photoreceptor outer segments by cultured retinal pigment epithelial cells.
The phagocytosis of photoreceptor outer segments (OS) by the retinal pigment epithelium (RPE) is a receptor mediated process. A key component of this process is the receptor tyrosine kinase, Mer. RPE cells from the RCS rat, which lacks a functional mer gene, and do not express Mer protein, are able to bind OS, but are unable to ingest them, suggesting that both a binding receptor and an ingestion receptor (Mer) are required for phagocytosis to occur. These rats become blind shortly after birth. To date the binding receptor has not been identified. Recent studies, using an SV40 transformed rat RPE cell line, RPE-J, or cultured human RPE cells, have suggested that the receptor for OS binding is the integrin alphavbeta5. However, the results presented here clearly show that this integrin plays at most a minor role in the phagocytosis of OS by primary cultures of rat RPE cells. OS phagocytosis by normal RPE cells is not affected by a function-blocking antibody to alphavbeta5 integrin, nor by the integrin-specific blocking peptide GRGDSP. Additionally, RPE-J cells do not express the Mer receptor protein, which has been shown to be obligatory for OS phagocytosis, or RPE65, a specific marker for RPE cells. We suggest that the RPE-J cell line is not a valid model with which to study the complex process of OS phagocytosis.
Hall
Michael O
MO
Jules Stein Eye Institute, UCLA Medical Center, 100 Stein Plaza, Los Angeles, CA 90095-7008, USA. hall@jsei.ucla.edu
Abrams
Toshka A
TA
Burgess
Barry L
BL
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D002352:Carrier Proteins; D002460:Cell Line; D004591:Electrophoresis, Polyacrylamide Gel / Q000379:methods; D005136:Eye Proteins; D005455:Fluorescent Antibody Technique / Q000379:methods; D015151:Immunoblotting / Q000379:methods; D016023:Integrins / Q000378:metabolism*; D009842:Oligopeptides / Q000378:metabolism; D010587:Phagocytosis / Q000276:immunology / Q000502:physiology*; D010857:Pigment Epithelium of Eye / Q000276:immunology / Q000502:physiology*; D011506:Proteins / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains; D019030:Receptors, Vitronectin / Q000378:metabolism*; D012374:Rod Cell Outer Segment / Q000276:immunology / Q000502:physiology*; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase
D000911:Antibodies, Monoclonal; D002352:Carrier Proteins; D005136:Eye Proteins; D016023:Integrins; D009842:Oligopeptides; D011506:Proteins; D019030:Receptors, Vitronectin; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase; C064660:integrin alphaVbeta5; C058161:glycyl-arginyl-glycyl-aspartyl-seryl-proline