Alpha‐2‐macroglobulin: A physiological guardian

Abstract Alpha macroglobulins are large glycoproteins which are present in the body fluids of both invertebrates and vertebrates. Alpha‐2‐macroglobulin (α 2 M), a key member of alpha macroglobulin superfamily, is a high‐molecular weight homotetrameric glycoprotein. α 2 M has many diversified and complex functions, but it is primarily known by its ability to inhibit a broad spectrum of proteases without the direct blockage of the protease active site. α 2 M is also known to be involved in the regulation, transport, and a host of other functions. For example, apart from inhibiting proteinases, it regulates binding of transferrin to its surface receptor, binds defensin and myelin basic protein, etc., binds several important cytokines, including basic fibroblast growth factor (bFGF), platelet‐derived growth factor (PDGF), nerve growth factor (NGF), interleukin‐1β (IL‐1β), and interleukin‐6 (IL‐6), and modify their biological activity. α 2 M also binds a number of hormones and regulates their activity. α 2 M is said to protect the body against various infections, and hence, can be used as a biomarker for the diagnosis and prognosis of a number of diseases. However, this multipurpose antiproteinse is not “fail safe” and could be damaged by reactive species generated endogenously or exogenously, leading to various pathophysiological conditions. J. Cell. Physiol. 228: 1665–1675, 2013. © 2012 Wiley Periodicals, Inc.