Disease relevance of Pzp

• Mice deficient in MAM and/or MUG thus offer new experimental models for defining in vivo the role of the macroglobulins in pancreatitis and in other normal and pathological processes [1].
• By incubating cells with both alpha 2 M-gold and vesicular stomatitis virus (VSV), we studied the internalization of these two markers simultaneously [2].
• Combined, these in vivo and in vitro findings demonstrate that the MAM contribute to the resistance of mice to acute myocarditis induced by experimental T. cruzi infection [3].
• To define their role in experimental Chagas disease, we investigated the susceptibility to T. cruzi infection of mice that are deficient only in alpha2-macroglobulins (AM-KO) or in both MAM and monomeric murinoglobulin-1 (MM-KO), relative to the wild type (WT) [3].
• Triggering and exacerbation of autoimmune arthritis by the Mycoplasma arthritidis superantigen MAM [4].

High impact information on Pzp

• The effect of dietary butylated hydroxyanisole (BHA) on methylazoxymethanol acetate [(MAM AC) CAS: 592-62-1; methyl-ONN-azoxy)methanol acetate]-induced intestinal carcinogenesis was studied in female CF1 mice [5].
• After cells to which alpha 2 M-gold had been bound at 0 degrees C were warmed, the gold was rapidly internalized into uncoated vesicles, previously termed receptosomes [2].
• Using transmission electron microscopy, we have studied the interaction of alpha 2 macroglobulin (alpha 2 M) with the surface of cultured fibroblasts [6].
• Because insulin and epidermal growth factor are internalized in the same structures as alpha 2 M (Maxfield, F.R., J. Schlessinger, Y. Schechter, I. Pastan, and M.C. Willingham. 1978. Cell, 14: 805--810.), we suggest that all peptide hormones, as well as other proteins that enter the cell by receptor-mediated endocytosis, follow this same pathway [6].
• We have previously characterized tumor-associated alpha 2-M synthesized and secreted by human tumor cell lines [7].

Biological context of Pzp

• The results demonstrate that MAM is expressed in the mouse embryo exclusively in the liver and not before day 13 of gestation [8].
• Northern blotting, reverse transcription and real-time-PCR, and in situ hybridization studies using C57Bl/6 mice revealed uterine induction of A2mp during decidualization and strong, midgestational association with modifying spiral arteries [9].
• However, statistically there was a strong correlation between the modal chromosome number and population doubling time (r2 = 0.88, P less than 0.001) and also between the modal chromosome number and alpha 2-M production (r2 = 0.73, P less than 0.01) [7].
• Here, we show that during T. cruzi infection (Y strain), the MAM and MUG hepatic mRNA levels and the corresponding plasma protein levels were up-regulated in C3H and C57BL/6 (B6) mice, but with different kinetics [10].
• Culture supernatants and highly purified MAM exhibited the same haplotype specificity (H-2k-dependent response) for stimulated proliferation of lymphocytes and for induction of interferon in vitro [11].

Anatomical context of Pzp

• Full-length cDNA for a mouse gene A2-macroglobulin induced by pregnancy (A2mp) was cloned from mesometrial decidua at Gestation Day 10 [9].
• Ligands such as alpha 2-M that are destined for lysosomal delivery reach a LAMP-1-positive organelle compartment only after they traverse LAMP-1-negative, non-lysosomal vesicles previously described as receptosomes [12].
• The present results indicate that receptor recognition of alpha 2M 'fast' forms by macrophages results in the rapid stimulation of eicosanoid secretion and suggest that secretion of prostaglandin E2 and other eicosanoids may be involved in the ability of alpha 2 M 'fast' forms to regulate various macrophage functional responses [13].
• We conclude that presentation of MAM to T cells is accomplished by E alpha-containing molecules [14].
• Of the E alpha-bearing progeny, there was a direct correlation between lymphocyte expression of F23.1 determinants and ability to respond to MAM [15].

Associations of Pzp with chemical compounds

• Transcripts of the meprin subunit truncated after the protease (alpha(1-275)), MAM (alpha(1-452)), and MATH (alpha(1-528)) domains or with individual domains deleted (DeltaMAM, DeltaMATH, and DeltaAM), were transfected into human embryonic kidney 293 cells [16].
• Studies by Johnstone and Coyle from the early 1980s have shown that treatment of pregnant rats with methylazoxymethanol acetate (MAM) results in the induction of neocortical microencephalopathy of the offsprings [17].
• Furthermore, interleukin-1-induced desensitization to TNF/GalN was not impaired in MAM(-/-) mice [18].
• The unique receptor actions and changes produced by streptozotocin suggest that extrinsic in addition to genetic factors influence the opioid receptor selectivity of heroin and 6 MAM [19].
• The reaction to SSA but not to MAM suggested the presence of sialic acid linked alpha2,6 to galactose in both cellular and serum TNX [20].

Other interactions of Pzp

• Mice deficient in either or both mouse alpha2-macroglobulin (MAM) and murinoglobulin-1 (MUG1) were generated and proved phenotypically normal under standard conditions [1].
• Northern analysis of adult tissues extended these observations: major signals for MAM and MUG were seen only in liver, while the expression of the alpha 2MR and the alpha 2MRAP/HBP-44 was widespread with highest levels of the 15-kb alpha 2MR mRNA in liver [8].

Analytical, diagnostic and therapeutic context of Pzp

• At early time points (0-5 min) after initiation of endocytosis, most structures containing alpha 2-M labeled with colloidal gold (receptosomes) were not labeled by anti-LAMP-1 detected using ferritin bridge or peroxidase immunocytochemistry [12].
• The antibodies were used in conjunction with commercially available rabbit antibody to alpha 2-M in a sandwich enzyme immunoassay [21].
• The monoclonal antibodies are also useful for immunocytochemistry and for immunoprecipitation of alpha 2-M [21].
• MAM was protease-labile, had pI greater than or equal to 9, and had Mr ca 15,000 according to gel filtration experiments [11].
• Although splenocytes from inbred C3H and CBA mice exhibited much higher proliferative responses to MAM than did those from B10.TRG.E alpha+ or B10.E alpha TG +/+ mice, flow cytometry showed similar levels of E alpha expression [14].

References