α-2-Macroglobulin (α-2M) is a homotetrameric serum protein consisting of four identical subunits that form dimers through disulfide bonds. Initially, α-2M was characterized as a pan-proteinase inhibitor that was able to "bait" proteinases into cleaving specific peptide sequences on α-2M. This interaction induces a conformational change in α-2M, thus enabling it to "trap" the proteinase and further inhibit its activity. Subsequently, α-2M has been shown to function as a carrier protein and regulator of cytokines during inflammation. Circulating transforming growth factor β (TGFβ) in serum is primarily bound to α-2M, which renders TGFβ inactive. α-2M also binds to IL-6 and, thereby, increases the concentration of IL-6 near lymphocytes, hepatocytes and stem cells involved in mediating the inflammatory cascade. Mutations and deletions in the gene encoding α-2M are associated with an increased incidence of Alzheimer's Disease (AD), which is consistent with the role of α-2M in mediating the clearance and degradation of A β, the major component of β-Amyloid deposits accumulated during AD.
Background References
1. Kotula E et al. DNA-PKcs plays role in cancer metastasis through regulation of secreted proteins involved in migration and invasion. Cell Cycle 14:1961-72 (2015).
2. Lund J et al. ADAMDEC1 is a metzincin metalloprotease with dampened proteolytic activity. J Biol Chem 288:21367-75 (2013).
Sequence Similarity
Belongs to the protease inhibitor I39 (alpha-2-macroglobulin) family.
Western blot analysis of A2M on human lung tissue lysates using anti-A2M antibody at 1/500 dilution.
Immunohistochemical analysis of paraffin-embedded human tonsil tissue tissue with Rabbit anti-A2M antibody (ET1703-69) at 1/50 dilution.
The section was pre-treated using heat mediated antigen retrieval with Tris-EDTA buffer (pH 9.0) for 20 minutes. The tissues were blocked in 1% BSA for 20 minutes at room temperature, washed with ddH2O and PBS, and then probed with the primary antibody (ET1703-69) at 1/50 dilution for 1 hour at room temperature. The detection was performed using an HRP conjugated compact polymer system. DAB was used as the chromogen. Tissues were counterstained with hematoxylin and mounted with DPX.
Immunohistochemical analysis of paraffin-embedded human liver tissue with Rabbit anti-A2M antibody (ET1703-69) at 1/200 dilution.
The section was pre-treated using heat mediated antigen retrieval with Tris-EDTA buffer (pH 9.0) for 20 minutes. The tissues were blocked in 1% BSA for 20 minutes at room temperature, washed with ddH2O and PBS, and then probed with the primary antibody (ET1703-69) at 1/200 dilution for 1 hour at room temperature. The detection was performed using an HRP conjugated compact polymer system. DAB was used as the chromogen. Tissues were counterstained with hematoxylin and mounted with DPX.
Immunohistochemical analysis of paraffin-embedded human spleen tissue with Rabbit anti-A2M antibody (ET1703-69) at 1/50 dilution.
The section was pre-treated using heat mediated antigen retrieval with Tris-EDTA buffer (pH 9.0) for 20 minutes. The tissues were blocked in 1% BSA for 20 minutes at room temperature, washed with ddH2O and PBS, and then probed with the primary antibody (ET1703-69) at 1/50 dilution for 1 hour at room temperature. The detection was performed using an HRP conjugated compact polymer system. DAB was used as the chromogen. Tissues were counterstained with hematoxylin and mounted with DPX.
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