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Effect of alpha2-macroglobulin on retinal glial cell proliferation
Ivan Milenkovic1, Gerd Birkenmeier, Peter Wiedemann
1Paul Flechsig Institute of Brain Research, University of Leipzig, Leipzig, Germany.
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.
