Human trabecular meshwork cells possess two distinct receptors for receptor-recognized forms of α2 macroglobulin
Purpose. α2-macro-globulin(α2M*) has been found to stimulate growth, regulate the synthesis and secretion of proteases and other compounds, and enhance antigen presentation in cells. We wanted to investigate the binding of receptor-recognized forms of α2M* to human trabecular meshwork (HTM) cells and study the effects of receptor binding, including internalization of the ligand and activation of intracellular signalling cascades. Methods. Direct binding studies with Scatchard analysis and internalization studies were performed to define α2M* ligand interactions with HTM cells. Changes in cellular 1,4,5-inositol triphosphate (IP3) and calcium(Ca2+) levels were also examined following stimulation with α2M* ligands. Immunoflouroescence studies were performed using anti-low-density-lipoprotein receptor-related protein/α2M* receptor(LRP) antibodies. Results. Two classes of α2M* binding sites are detectable on HTM cells, 1600 sites with an apparent Kd= 20 pM and 31,800 sites with an apparent Kd=5 nM for α2M* binding. α2M* is internalized by HTM cells, and LRP is detectable on HTM cell surfaces. Exposure of HTM cells to α2M* elicits increases in the intracellular levels of IP3 and Ca2+. Conclusions. HTM cells possess two distinct receptors for α2M*. In situations of proteolysis, HTM cells can clear α2M-protease complexes as well as respond to the presence of the complexes via the activation of signaling cascades. The presence of specific α2M* receptors on HTM cells suggests a role for α2M* in the physiology of the anterior chamber of the eye.
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Related Subject Headings
- Ophthalmology & Optometry
- 3212 Ophthalmology and optometry
- 11 Medical and Health Sciences
- 06 Biological Sciences
Citation
Published In
ISSN
Publication Date
Volume
Issue
Related Subject Headings
- Ophthalmology & Optometry
- 3212 Ophthalmology and optometry
- 11 Medical and Health Sciences
- 06 Biological Sciences