01.08.2005 | Laboratory Investigation
Effect of α2-macroglobulin on retinal glial cell proliferation
Graefe's Archive for Clinical and Experimental Ophthalmology
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Activation of the receptor for α2-macroglobulin (α2M), the low-density lipoprotein-related protein (LRP1; CD91), has been suggested to represent a possible strategy for the inhibition of uncontrolled retinal cell proliferation via stimulation of the clearance of α2M-bound growth factors and proteinases from the extracellular space. In order to prove this assumption, we investigated the effect of α2M on the proliferation of Müller glial cells in vitro.
Proliferation assays using bromodeoxyuridine were carried out on cultured Müller glial cells of the guinea pig in the absence and presence of α2M.
Activated α2M evoked a slight increase of the cell proliferation at control conditions. Addition of α2M to the culture medium inhibited the proliferation evoked by agonists of G-protein-coupled receptors [adenosine 5′-triphosphate (ATP), neuropeptide Y]. However, α2M did not diminish the proliferation evoked by agonists of receptor tyrosine kinases (epidermal and platelet-derived growth factors) and by serum, respectively. Inhibition of LRP1 by a neutralizing antibody did not alter the ATP-evoked proliferation while it increased the proliferation in the presence of α2M.
It is concluded that α2M inhibits the proliferation evoked by agonists of G-protein-coupled receptors, possibly via enhanced growth factor clearance by LRP.