Effect of alpha2-macroglobulin on retinal glial cell proliferation.
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.


CONCLUSIONS
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.
Milenkovic
Ivan
I
Paul Flechsig Institute of Brain Research, University of Leipzig, Leipzig, Germany.
Birkenmeier
Gerd
G
Wiedemann
Peter
P
Reichenbach
Andreas
A
Bringmann
Andreas
A
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001973:Bromodeoxyuridine; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D004815:Epidermal Growth Factor / Q000494:pharmacology; D006168:Guinea Pigs; D008297:Male; D009457:Neuroglia / Q000166:cytology*; D009478:Neuropeptide Y / Q000494:pharmacology; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000819:agonists; D012160:Retina / Q000166:cytology*; D000511:alpha-Macroglobulins / Q000494:pharmacology*
D009478:Neuropeptide Y; D010982:Platelet-Derived Growth Factor; D043562:Receptors, G-Protein-Coupled; D000511:alpha-Macroglobulins; D004815:Epidermal Growth Factor; D000255:Adenosine Triphosphate; D011505:Protein-Tyrosine Kinases; D001973:Bromodeoxyuridine