The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1999/9/861/ $5.00
The Journal of Experimental Medicine, Volume 190, Number 6, September 20, 1999 861-874

Macrophage and Retinal Pigment Epithelium Phagocytosis: Apoptotic Cells and Photoreceptors Compete for {alpha}vß3 and {alpha}vß5 Integrins, and Protein Kinase C Regulates {alpha}vß5 Binding and Cytoskeletal Linkage

Silvia C. Finnemanna and Enrique Rodriguez-Boulana
a Department of Ophthalmology and Department of Cell Biology, Margaret M. Dyson Vision Institute, Weill Medical College of Cornell University, New York, New York 10021

Correspondence to: Silvia C. Finnemann, Margaret M. Dyson Vision Research Institute, Box 233, Department of Ophthalmology, Weill Medical College of Cornell University, 1300 York Ave., New York, NY 10021. Tel:212-746-2271 Fax:212-746-8101 E-mail:sfinne{at}mail.med.cornell.edu.

Noninflammatory monocyte macrophages use {alpha}vß3 integrin to selectively bind apoptotic cells, initiating their phagocytic removal. In a related process, the retinal pigment epithelium (RPE) employs {alpha}vß5 integrin to recognize spent photoreceptor outer segment particles (OS). Here, we show that apoptotic cells and OS compete for binding to these receptors, indicating that OS and apoptotic cells expose surface signals recognizable by {alpha}vß3 and {alpha}vß5. Particle binding to {alpha}vß5 required protein kinase C (PKC) activation. In RPE, {alpha}vß5 binding was maximally activated even before any phagocytic challenge and was reduced by PKC inhibitors. In macrophages, it was dormant but became activated upon PKC stimulation. PKC-activated {alpha}vß5-mediated binding in macrophages differed from constitutive binding to the same integrin receptor in RPE cells in that the former followed much faster kinetics, similar to particle binding mediated by {alpha}vß3. Activation of {alpha}vß5 for particle binding correlated with its recruitment into a detergent-insoluble fraction, a process sensitive to pharmacological modulation of PKC in both types of phagocytes. Furthermore, {alpha}vß5 but not {alpha}vß3 particle binding required actin microfilaments. These data constitute the first evidence that noninflammatory phagocytes actively regulate the earliest phase of phagocytic clearance, particle binding, by controlling receptor activity.

Key Words: phagocytosis, recognition, integrins, macrophages, retinal pigment epithelium


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