Increased binding of concanavalin a to α2-macroglobulin, IgM and IgG from cystic fibrosis plasma

Shapira, Emmanuel; Menendez, Roger

doi:10.1016/s0006-291x(80)80244-0

Cited by 18 publications

(7 citation statements)

References 10 publications

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“…Abnormalities in exocrine gland secretion, proteolytic enzymes and their inhibitors, polyamine metabolism and the presence of factors presumably unique to CF have been described and reviewed (17,22). Abnormalities in some aspects of glycoprotein metabolism as the possible underlying defect in CF have been suggested (1, 4,23,29).…”

Section: Speculationmentioning

confidence: 99%

“…More recently, functional (25,26,28) and structural (4, 33) alterations in alpha-2-macroglobulin, a serum glycoprotein, were documented. Increased binding of the lectin concanavalin A to alpha-2-macroglobulin as well as to immunoglobulin G and to immunoglobulin M from CF patients was also observed (29). Alhadeff et al (2) documented an altered carbohydrate moiety of the lysosomal enzyme alpha-fucosidase from CF patients.…”

mentioning

confidence: 95%

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A Purified Serum Glycopeptide from Controls and Cystic Fibrosis Patients. I. Comparison of their Mucociliary Activity on Rabbit Tracheal Explants

Blitzer

Shapira

1982

Pediatr Res

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Section: Speculationmentioning

confidence: 99%

mentioning

confidence: 95%

A Purified Serum Glycopeptide from Controls and Cystic Fibrosis Patients. I. Comparison of their Mucociliary Activity on Rabbit Tracheal Explants

Blitzer

Shapira

1982

Pediatr Res

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“…This study has not addressed the possibility that altered carbohydrate side chains of asM may occur in C F azM as has been recently suggested by others (4,26). However, such alterations, if they exist, do not appear to affect the major structural features of a2M.…”

Section: +-mentioning

confidence: 76%

Comparison of the Structure and Aspects of the Proteinase-Binding Properties of Cystic Fibrotic α2-Macroglobulin with Normal α2-Macroglobulin

et al. 1982

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SummaryConsiderable attention has been focused recently on a2-macroglobulin (LYZM), a major endopeptidase inhibitor in blood plasma, as a possible source of the primary defect in cystic fibrosis (CF). We report here studies designed to compare the structure of CF a z M with normal a2M to determine if there is a difference. The physicochemical properties of purified a2M as revealed by various electrophoretic techniques, covalent proteinase binding properties, and primary structural studies on a variety of partial hydrolyzates of CF azM and normal a2M are compared. These studies were carried out on eight different individual isolates of CF a2M and three age-matched normal a z M preparations and a2M isolated from fetal cord blood. Three properties of CF aZM were studied by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE): (1) the existence of four identically-sized subunits in the native molecule (lo), (2) the cleavage of this subunit into fragments of approximately 100,000 daltons upon interaction with proteinases (lo), and (3) the cleavage of an alkaline/heat sensitive bond to produce 120,000 and 60,000 dalton fragments (11). Both CF and normal azM were cleaved to the extent of 79-87%. CF a2M behaves identically with normal azM with regard to all these properties. Salvesen and Barrett (24) have demonstrated that varying proportions of several [12511-labeled proteinases form SDSstable, non-reducible links to normal a2M. TWO of the CF a2M preparations were studied to determine if similar covalent binding of proteinases occurred. The positions of the labeled and % of proteinase bound bands in SDS/reduced PAGE system were identical for normal a2M and CF azM. These results indicate that CF (YZM behaves normally with regard to covalent binding of proteinases. Qualitative comparison of the peptide fragments separated by SDS-PAGE or isoelectric focusing of CF and normal a z M produced by partial proteolysis with trypsin, chymotrypsin or Staphylococcus aureus V-8 proteinase did not reveal any differences unique to CF a2M. The cyanogen bromide fragmentation studies and the cysteine cleavage studies also indicated that no major change in the positions of methionyl residues or cysteinyl/cystinyl residues has occurred in CF a2M. The failure of all these different studies and those reported by others to demonstrate any differences between CF and normal a2M makes it highly unlikely that there is a primary defect in a Z M in CF.

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“…Other investigators have also reported previously that proteolysis of C5 and C3 generates fragments with chemotactic activity (5,17,18 (1,2); and (c) normal cultures might be expected to produce significant amounts of both of the CDS chemoattractants since they contain detectable quantities of the C5 fragment without ciliary dyskinesia activity (Fig. 2) serum, and cell culture medium from CF genotypes are deficient in serine protease activity (as compared to analogous fluids from normal controls), and the findings of Shapira and co-workers (20 and references cited therein) and Wilson and Fudenberg (21), which collectively indicate that alpha2-macroglobulin, a major protease regulator synthesized by alveolar MO and monocytes (22,23), is abnormal in CF with respect to both its carbohydrate structure (20) and its ability to regulate serine proteases (20,21). We speculate that the findings of Walsh and co-workers reflect a more fundamental defect in CF alpha2-macroglobulin (24).…”

Section: Discussionmentioning

confidence: 90%

Cystic fibrosis ciliary dyskinesia substances and pulmonary disease. Effects of ciliary dyskinesia substances on neutrophil movement in vitro.

Wilson¹,

Fudenberg²,

Parise³

et al. 1981

J. Clin. Invest.

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A B S T R A C T Cultured mononuclear cells (MNC) from individuals homozygous or heterozygous for the defective gene causing the inherited disease cystic fibrosis (CF) synthesize three unusual "mediators" termed ciliary dyskinesia substances (CDS), which markedly affect tracheal mucociliary systems in vitro. MNC cultures from normal healthy controls do not accumulate any CDS, whereas MNC cultures from non-CF patient controls with pulmonary disease synthesize at least one CDS. The possible involvement of the CDS in pulmonary disease is being investigated. In this study, we sought to determine whether the CDS could be chemoattractants for polymorphonuclear neutrophils (PMN), since they have characteristics in common with known chemoattractants generated by alveolar macrophages. Our

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Increased binding of concanavalin a to α2-macroglobulin, IgM and IgG from cystic fibrosis plasma

Cited by 18 publications

References 10 publications

A Purified Serum Glycopeptide from Controls and Cystic Fibrosis Patients. I. Comparison of their Mucociliary Activity on Rabbit Tracheal Explants

A Purified Serum Glycopeptide from Controls and Cystic Fibrosis Patients. I. Comparison of their Mucociliary Activity on Rabbit Tracheal Explants

Comparison of the Structure and Aspects of the Proteinase-Binding Properties of Cystic Fibrotic α2-Macroglobulin with Normal α2-Macroglobulin

Cystic fibrosis ciliary dyskinesia substances and pulmonary disease. Effects of ciliary dyskinesia substances on neutrophil movement in vitro.

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