Disease relevance of A2M

• Isolation and characterization of alpha 2-macroglobulin from mastitis milk [1].

High impact information on A2M

• Double-label experiments using beta-galactosidase and gold/alpha 2-macroglobulin showed the presence of the two ligands in the same coated pits and receptosomes [2].
• Thus, the pathway for internalization of beta-galactosidase via the mannose 6-phosphate receptor is similar to the pathway established for other ligands such as low density lipoprotein and alpha 2-macroglobulin [2].
• The addition of alpha 2-macroglobulin to serum-free medium or to antiprotease-depleted serum resulted in the blockage of morphological responses of Sertoli cells to FSH or to dbcAMP [3].
• Addition of alpha 2-macroglobulin blocked the inhibitory effects of dbcAMP on Sertoli cell migration [3].
• The conformational changes around the thioester-bond region of human or bovine alpha 2M (alpha 2-macroglobulin) on reaction with methylamine or trypsin were studied with the probe AEDANS [N-(acetylaminoethyl)-8-naphthylamine-1-sulphonic acid], bound to the liberated thiol groups [4].

Biological context of A2M

• We found that active fetuin preparations did contain alpha 2-macroglobulin that stimulated smooth muscle cell growth [5].
• In addition, binding of 125I-transferrin to cells was saturable at 4 degrees C. These studies indicate that transferrin and alpha 2-macroglobulin are taken up by receptor-mediated endocytosis [6].
• Chemical deglycosylation reveals that it is composed of two different subunits, designated A and B. The N-terminal amino-acid sequence of subunit A is similar to the N-terminus of invertebrate alpha-2-macroglobulin [7].
• The albumin/alpha 2-macroglobulin ratio increased by 6.8 in the first milking to 44.4 at 2 wk postpartum, indicating that the increase of alpha 2-macroglobulin was greater than that of albumin [8].
• Time-course levels of alpha 2-macroglobulin and albumin in cow's colostrum and milk during lactation were investigated in order to obtain data that could help to elucidate the biological role of alpha 2-macroglobulin in mammary secretions [8].

Anatomical context of A2M

• We conclude that the principal mitogenic component for smooth muscle cells in crude fetuin preparations is PDGF, since purified bovine alpha 2-macroglobulin or fetuin do not appreciably affect growth of these cells [5].
• Thus, the diminution in bundles of F-actin containing stress fibers, which otherwise takes place in Sertoli cells stimulated by FSH or by dbcAMP, did not occur in cells in culture in the presence of alpha 2-macroglobulin, in the presence or absence of acid-treated serum [3].
• Only alpha 2-macroglobulin was transferred into lysosomes, whereas transferrin was recycled to the cell surface [6].
• 6. The broad spectrum antiproteinase alpha 2-macroglobulin achieved almost total ablation of the action of stimulated eosinophils in the bronchial mucosa [9].
• Receptor-mediated endocytosis of alpha 2-macroglobulin and transferrin in rat caput epididymal epithelial cells in vitro [6].

Associations of A2M with chemical compounds

• Its enzymatic nature was verified using protease inhibitors, including N-ethylmaleimide, phenylmethylsulfonyl fluoride, o-phenanthroline, and EDTA, as well as pepstatin A and alpha 2-macroglobulin [10].
• The residues contributing to the thioester bonds in bovine alpha 2-macroglobulin were differentially labelled by modification of the Glu moiety with [14C]methylamine and of the Cys moiety with iodo[3H]acetate [11].
• Since alpha 2-macroglobulin does not bind heparin, it follows that VEGF165 does not bind O-desulfated heparin efficiently [12].
• Anti-TGF beta antibodies could reverse the inhibition caused by the acid/ethanol extract but not that caused by native alpha 2M [13].
• We observed that commercial preparations of bovine plasma alpha 2M were able to mimic the inhibitory action of TGF beta on adrenocortical cortisol production, with the same specificity of action directed at the steroid 17 alpha-hydroxylation step [13].

Physical interactions of A2M

• Possibly kallikrein or a related trypsin-like enzyme is bound to alpha 2-macroglobulin and is not free to react with the inhibitors [14].

Other interactions of A2M

• We also observed that adrenocortical cells secrete TGF beta 1 under a latent form together with large amounts of alpha 2-macroglobulin, a protease inhibitor known to be implied in the latency of TGF beta in serum [15].
• Heparin and N-desulfated heparin efficiently inhibited the binding of 125I-VEGF165 to alpha 2-macroglobulin, but surprisingly, O-desulfated heparin was an ineffective inhibitor [12].
• The binding of bovine S protein to S dysgalactiae isolates was specific and could not be inhibited by other plasma proteins, such as fibronectin, albumin, fibrinogen, alpha 2-macroglobulin, or IgG [16].
• Similar alterations in the levels of the inhibitory proteins antithrombin III and alpha 2-macroglobulin were observed [17].
• In addition, alpha 2-macroglobulin, but not alpha 1-antitrypsin, inhibits the action of the proteinases [18].

Analytical, diagnostic and therapeutic context of A2M

• Gel filtration experiments demonstrated that in Pedersen fetuin PDGF occurred both free, and in association with alpha 2-macroglobulin [5].
• Conformational alterations occurring in bovine alpha 2-macroglobulin (alpha 2M) resulting from proteolysis and nucleophilic modification have been monitored by UV difference spectra, circular dichroism, and changes in the fluorescence of 6-(p-toluidino)-2-naphthalenesulfonate (TNS) and bis(8-anilino-1-naphthalenesulfonate) (Bis-ANS) [19].
• Sequence analysis of several internal peptides confirms that the tick protein belongs to the alpha-2-macroglobulin family, and the protein is therefore referred to as tick alpha-macroglobulin (TAM) [7].
• We cloned and sequenced a PCR product containing sequences from both subunits and spanning the N-terminus of subunit B and the putative 'bait region' (a segment of alpha-2-macroglobulin which serves as target for various proteases) [7].
• The immunoassay was affected both by alkaline denaturation, which is a common feature of aspartic proteinases, and by the presence of the proteinase scavenger alpha-2-macroglobulin [20].

References