BACKGROUND: Activation of the receptor for alpha2-macroglobulin (alpha2 M), 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 alpha2 M-bound growth factors and proteinases from the extracellular space. In order to prove this assumption, we investigated the effect of alpha2 M on the proliferation of Müller glial cells in vitro. METHODS: Proliferation assays using bromodeoxyuridine were carried out on cultured Müller glial cells of the guinea pig in the absence and presence of alpha2 M. RESULTS: Activated alpha2 M evoked a slight increase of the cell proliferation at control conditions. Addition of alpha2 M to the culture medium inhibited the proliferation evoked by agonists of G-protein-coupled receptors [adenosine 5'-triphosphate (ATP), neuropeptide Y]. However, alpha2 M 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 alpha2 M. CONCLUSION: It is concluded that alpha2 M inhibits the proliferation evoked by agonists of G-protein-coupled receptors, possibly via enhanced growth factor clearance by LRP.
BACKGROUND: Activation of the receptor for alpha2-macroglobulin (alpha2 M), 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 alpha2 M-bound growth factors and proteinases from the extracellular space. In order to prove this assumption, we investigated the effect of alpha2 M on the proliferation of Müller glial cells in vitro. METHODS: Proliferation assays using bromodeoxyuridine were carried out on cultured Müller glial cells of the guinea pig in the absence and presence of alpha2 M. RESULTS: Activated alpha2 M evoked a slight increase of the cell proliferation at control conditions. Addition of alpha2 M to the culture medium inhibited the proliferation evoked by agonists of G-protein-coupled receptors [adenosine 5'-triphosphate (ATP), neuropeptide Y]. However, alpha2 M 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 alpha2 M. CONCLUSION: It is concluded that alpha2 M inhibits the proliferation evoked by agonists of G-protein-coupled receptors, possibly via enhanced growth factor clearance by LRP.
Authors: Vanessa Moll; Michael Weick; Ivan Milenkovic; Hannes Kodal; Andreas Reichenbach; Andreas Bringmann Journal: Invest Ophthalmol Vis Sci Date: 2002-03 Impact factor: 4.799
Authors: Ivan Milenkovic; Michael Weick; Peter Wiedemann; Andreas Reichenbach; Andreas Bringmann Journal: Invest Ophthalmol Vis Sci Date: 2003-03 Impact factor: 4.799
Authors: Gordon W Laurie; Leslie A Olsakovsky; Brian P Conway; Robert L McKown; Kazuko Kitagawa; Jason J Nichols Journal: Optom Vis Sci Date: 2008-08 Impact factor: 1.973