Proteins, proteomics

alpha 2-macroglobulin

Alpha-2 macroglobulin (A2M), α-2 macroglobulin is an an acute phase protein synthesized in response to pro-inflammatory cytokines early in the inflammatory response.

A2M is a large plasma protein produced by the liver, and is a major component of the alpha-2 band in protein electrophoresis. A2M interacts and captures virtually any proteinase whether self or foreign, suggesting a function as a unique "panproteinase inhibitor." A2M also removes the active forms of the gelatinase (MMP-2 and MMP-9) from the circulation, binding to scavenger receptors on the phagocytes. In the mechanism termed "clearance of activated alpha 2-macroglobulin", ACT undergoes Ca(2+)-dependent binding to a member of the low-density lipoprotein receptor supergene family that mediates cellular uptake by endocytosis and delivery to endosomes and lysosomes. Thus, the peptide binding function of A2M allows targeting of biologically active peptides to different cell types expressing the A2M receptor. Complexes internalized through this binding may be dispatched into different pathways of endocytic/lysosomal pathways in a cell type-specific manner.[r]

A2M ratios are increased in nephrotic syndrome when the kidneys lose smaller plasma proteins (proteinuria). A common variant of α2-macroglobulin is associated with increased risk of Alzheimers disease.

 Scavenger Receptors


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. . . since 11/21/06