SEARCH · PubMed Health
Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
In vitro Kallikrein inhibits the expression of lymphocytes-E-rosetting-receptor. The preincubation of alpha-2-macroglobulin with Kallikrein prevents this effect quickly. The incubation with alpha-2-macroglobulin of Kallikrein pretreated-lymphocytes is ineffective.
By using Laser nephelometry concentration of alpha 2-macroglobulin and alpha 1-antitrypsin in amniotic fluid was measured in early pregnancy (15th-24th week) and near term (after 37th week). alpha 2-macroglobulin was demonstrable in all cases, concentration of specimen after 37th week were significantly higher than in early pregnancy. Concentration of alpha 1-antitrypsin changes during pregnancy similar to total protein and albumin concentrations.
During trypsin perfusions in normal rabbits and in rabbits in acute phase reaction (APR), there is no modification in cardiorespiratory functions except in the instant preceding death. The fibrinogen level decreases and fibrin is deposited in the vascular lumen. The alpha 2 macroglobulin (alpha 2 M) content diminishes more rapidly than the alpha I macroglobulin (alpha I M) content; moreover, in subjects in APR, the decrease of alpha I M is further slowed with increasing perfusion rates, whereas the decrease in alpha 2 M remains constant. All the alpha M are completely combined at death. Therefore, it can be assumed that only the hepatic filtering of the alpha I M enzyme complex is subject to saturation.
This is the third report in a series on the inflammatory mediators and modulators released in organ culture from skin lesions of various ages, which were produced in vivo in rabbits by the military vesicant, sulfur mustard (SM). It describes the electrophoretic protein fractions and trypsin-inhibitory capacities of the various culture fluids and the amounts of alpha 1-proteinase inhibitor and alpha-macroglobulin proteinase inhibitors in these fluids. With one-dimensional electrophoresis, the albumin and beta-globulin fractions of protein in culture fluids varied little with the development and healing of the SM lesions. These fractions proportionally resembled the corresponding fractions found in serum. The alpha 1-globulin fraction was proportionally smaller than the corresponding fractions of serum as the lesions healed. The alpha 2-globulin fraction was proportionally smaller than the corresponding fractions of serum at all stages of lesion development and healing. The gamma-globulin fraction was proportionally larger as the lesions healed. With two-dimensional electrophoresis, about 68%, 46%, and 35% of the protein spots in culture fluids from representative 1-day and 6-day SM lesions and normal skin, respectively, matched those from serum. In each case, the large, diffuse, serum albumin spot represented about two-thirds of the protein present. Thus, gravimetrically, in normal skin and in both developing and healing lesions, the extracellular proteins were 80-90% of serum origin. The trypsin-inhibitory capacity (TIC) per milligram protein in the culture fluids of healing lesions was markedly less than the TIC per milligram protein in the fluids of peak lesions. This decrease correlates well with the decrease found in the alpha 1-globulin fraction, which contains alpha 1-antiproteinase (alpha 1-PI) (and alpha 1-macroglobulin [alpha 1M] in rabbits). The alpha 1PI and the alpha 1M-alpha 2M proteinase inhibitors were identified in the culture fluids by means of sodium dodecyl sulfate-polyacrylamide gel electrophoresis, Western blots, specific antibodies, and the immuno-peroxidase technique. The levels of both free and proteinase-complexed alpha 1PI and alpha M inhibitors in the culture fluids decreased as the lesions healed. In both developing and healing lesions, at least half of the alpha 1PI and alpha M inhibitors seemed to be complexed with proteinases. Thus, serum seems to be a major source of unbounded extracellular protein within acute inflammatory lesions, and serum proteinase inhibitors seem to be the host's major defense against local damage by proteinases from serum, infiltrating leukocytes, and activated fibroblasts.
The interaction rat liver microsomes/human alpha 2 macroglobulin releases in vivo an inhibitory peptide of the hepatocyte proliferation. Treatment of Triton X 100 on adult rat liver microsomes enables the solubilisation of a proteolytic enzyme. Its partial purification was obtained by Ultrogel AcA 44 filtration followed by a DEAE Sephacel chromatography. This enzyme shows a proteolytic activity in presence of calcium on synthetic substrates including Phe, Tyr and Trp. A whole enzyme inhibition is got after treatment by DFP or benzamidine. In presence of highly purified human alpha 2 macroglobulin this enzyme releases a glycopeptide of low molecular weight, which inhibits the hepatocyte proliferation during the G1-S transition in baby rat.
Content of alpha 1-antitrypsin and alpha 2-macroglobulin was studied in blood serum of patients with acute and chronic forms of pneumonia. Within the first decade of the disease alpha 1-antitrypsin was more distinctly increased in the patients with chronic pneumonia. Stable elevation of alpha 1-antitrypsin correlated with long-term presence of the inflammation symptoms. Content of alpha 2-macroglobulin was slightly decreased during the disease.
Digestion of human alpha 2-macroglobulin-methylamine (alpha 2M-CH3NH2) with papain prior to gel filtration resulted in the resolution of three distinct peaks. The material in peak I (Mr approximately 600,000) and peak II (Mr approximately 55,000) did not have any receptor binding ability as determined by in vivo clearance studies and in vitro competitive binding studies using mouse peritoneal macrophages. In contrast, the material in peak III (Mr approximately 20,000) bound to macrophage alpha 2-macroglobulin (alpha 2M) receptors with a Kd of 250 nM. This represents a 500-fold decrease in affinity relative to undigested alpha 2M-CH3NH2. Sequence analysis demonstrated that this material constituted the carboxyl-terminal fragment (COOH-terminal fragment) of alpha 2M. alpha 2M is known to possess a methionyl residue which is susceptible to modification by cis-dichlorodiammineplatinum (II) (cis-DDP) with the result being a loss of receptor binding ability by alpha 2M. For this reason, experiments were performed to determine if the platinum-reactive methionyl residue is located in the COOH-terminal receptor binding fragment of alpha 2M. The results of this investigation demonstrate that cis-DDP is not reactive with either the isolated COOH-terminal fragment or the COOH-terminal fragment isolated from alpha 2M-CH3NH2 which had been pretreated with cis-DDP. In addition, the COOH-terminal fragment did not bind to monoclonal antibody 7H11D6, a monoclonal antibody which binds to the platinum-reactive epitope of the alpha 2M-CH3NH2 receptor recognition site. In contrast, the 55-kDa fragment of alpha 2M bound approximately 1 mol platinum/mol of 55-kDa fragment and also bound to monoclonal antibody 7H11D6. Since the COOH-terminal fragment retains some receptor binding ability, the results of this investigation demonstrate that this fragment is not the complete receptor recognition site and suggest that a platinum-reactive methionyl residue located in the 55-kDa fragment of alpha 2M is another component of this site.
Interspecific variability of the isotypic structure of two macroglobulins (Lpm and alpha 2M) in Mustelidae family was investigated using monospecific rabbit antisera against Lpm and alpha 2M Mustela vison. It was established that all the species studied may be divided into four groups, according to the degree of their homology with Lpm: 1) M. vison; 2) M. altaica, M. erminea, Kolonocus sibirica, Putorius eversmany, P. putorius, Luteola lutreola; 3) Vormela peregusna; 4) Martes martes, M. foina, M. zibellina. The greatest divergence of Martes gene species from M. vison and other species studied is determined by two different immunogenetic approaches, the first based on the whole isotype of Lpm and the other using allotypic markers of individual Lpm genes. The variability of the isotypic structure of alpha 2M was lower than that revealed in Lpm. V. peregusna is the only species which significantly differs from all above-mentioned species, including M. vison. The differences established for degree of variability between Lpm and alpha 2M in Mustelidae family may be connected with the evolutionary peculiarities of these two genetic system of serum alpha-macroglobulins, which being phylogenetically related, are still structurally divergent.
The study of two proteins, acute phase reactants, alpha 1-proteinase inhibitor and alpha 2-macroglobulin, has demonstrated their utility in the diagnosis of the activity of ulcerative colitis. Alpha 1-proteinase inhibitor presented serum increases parallel to the degree of activity, permitting differentiation of asymptomatic, mild, moderate and severe phases of the disease. Increases in alpha 2-macroglobulin coincided with less-intense phases of the disease. The possible biological basis of this different behavior is discussed, as well as its potential inclusion among the biological tests currently used in clinical practice.
Alpha 2-Macroglobulin concentrations as measured by a functional assay and by laser nephelometry with antibody precipitation were compared for 67 outpatients at a respiratory clinic and 30 blood-donor control subjects with no respiratory disease. In both groups, concentrations of alpha 1-protease inhibitor in plasma, as measured by laser nephelometry, were within the normal reference interval. A reasonable correlation (r = 0.70) was obtained between results of functional assays and of laser nephelometry for the control individuals. For patients with pulmonary disease the correlation between the two assay methods was poorer (r = 0.53). We conclude that the functional assay of plasma is the better method for detecting abnormal concentrations of alpha 2-macroglobulin in patients with lung diseases.
Combination of two procedures--pseudoligand affinity chromatography on Cibacron blue agarose and usual gel filtration on TSK HW-60 enabled to separate successfully blood plasma alpha 2-macroglobulin from immunoglobulin M, haptoglobins and low molecular weight proteins. The preparation of alpha 2-macroglobulin obtained exhibited high inhibitory activity towards proteases.
In the serum of 21 women with malignant ovarian tumours, 13 with uterine myomas and 16 with cysts the concentrations were determined of alpha 1 inhibitor of proteases and alpha 2 macroglobulin by immunodiffusion, and the functional activity of both inhibitors which made possible calculation of the specific activity (units of inhibitory activity per one gram of inhibitor protein). In women with malignant tumours the specific activity of alpha 1 inhibitor was decreased, suggesting that a part of the inhibitor was functionally inactive. This decrease was statistically significant in relation to the control group and the groups of myomas and cysts, but was independent of the degree of disease progression. The specific activity of alpha 2 macroglobulin was significantly decreased only in patients with grade IV degrees of clinical progression (according to FIGO) in relation to the control group and to the group with cysts.
125I-labelled alpha 2-macroglobulin complexed with trypsin bound to human cancer cell lines (HTB 144, CRL 1427, CCL 30, HB 8065, CCL 2, CRL 1593) but to a lesser degree than to normal cells. Malignant transformation of murine BALB/c 3T3 cells with Kirsten sarcoma virus caused a 50% reduction in the alpha 2-macroglobulin-trypsin complex binding. Two cloned revertants derived from the malignant BALB/c 3T3 cells did not induce tumors upon syngrafting. One exhibited normal binding and the other reduced binding. A reduced alpha 2M-proteinase complex binding is thus common in tumor cells but is not a unique property of the malignant state.
Using chromatographic technique on "Sephadex G 200" associated to immunologic qualitative and quantitative techniques, the authors showed that the alpha1-macroglobulin is present in normal Rat urines. This protein is also present in urines obtained during the Masugi nephritis. The alpha1-macroglobulin concentration observed in the different urine samples is unrelated to the total proteinuria evolution. The results given allow us to discuss the mechanisms of the glomerular filtration.
The serum and synovial fluid concentrations of alpha2 macroglobulin and alpha2 neuramino glycoprotein of patients with rheumatoid arthritis have been studied. For, both protein fractions have antiprotease activity and inhibit, though to different degrees, many factors concerning inflammation. Even though both fractions have certain activities in common, in rheumatoid arthritis, we neither see a parallel increase nor antagonistic actions in the case of alpha2 macroglobulin and alpha2 neuramino-glycoprotein.
The high levels of alpha 2-macroglobulin found in the serum of three patients suffering from Dyggve-Melchior-Clausen syndrome, an autosomal recessive metabolic disorder, resembling mucopolysaccharidoses, have been further characterised by crossed immunoelectrophoresis. The immunoprecipitate of patients' alpha 2-macroglobulin forms a double arc, this may be helpful in the diagnosis of the syndrome.
Slices of rat liver or Morris Hepatomas 5123 GVI and 7777 were incubated for 2 h with 14C-leucine. Newly synthesized labelled proteins were determined independently in the medium and tissue homogenate, total protein after precipitation with trichloro-acetic acid, and albumin, fibrinogen and alpha 2-macroglobulin after immuno-precipitation with monospecific antisera. In comparison with control rat liver, synthesis and secretion of albumin were reduced four- to five-fold in the 2 heptomas examined. On the other hand, synthesis and secretio of fibrinogen and alpha 2-macroglobulin in Hepatomas 5123 GVI annd 7777 were similar to rat liver, especially to the liver isolated from rats with turpentine-induced local inflammation.
The supernatant of 'crowded' but not 'spread' rabbit spleen cell cultures contains a macroglobulin factor which behaves in an Ig-turnover assay as any T-independent antigen or polyclonal B-cell activator (PBA). In the supernatants of crowded rabbit lymphoid cell cultures prepared in serum free medium, the factor was found to be associated entirely with the alpha-macroglobulin (alpha M) fraction (alpha 1 + alpha 2). This alpha M was most probably actively secreted by the lymphocytes because: (i) sequential supernatants obtained in serum free medium of crowded cultures contained equal amounts of alpha M as well as equal PBA activity; (ii) the alpha M became labelled when the cells were grown in medium containing a radioactive amino acid. Macrophages were not required for the production of PBA. PBA was not produced when either crowded B or T cells were cultured alone but only when they were cultured together. Purified T cells were not triggered by any plant lectin to produce PBA. By use of anti-alpha 2M allotype antibodies and B and T cells from different rabbits, the PBA was shown to have the allotype of the T-cell donor. The PBA was associated with rabbit alpha 2M but not alpha 1M. We concluded that upon close contact, B cells stimulate T cells to produce a PBA associated with alpha 2M.