α2-Macroglobulin and Related Thiol Ester Plasma Proteins

Sottrup‐Jensen, Lars

doi:10.1016/b978-0-12-568405-7.50010-2

Cited by 103 publications

(84 citation statements)

References 662 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…3 and 4), Cl forms, along with a2M, were the main defensin-binding compartments. At the high level found in the plasma of septic patients, defensins may chiefly bind to and be disposed of by a2M [3] the concentration of which in human blood (24 PM) is much higher than that of Cl complement [22]. Human serum albumin, the major anionic protein of human blood, did not compete with defensin binding to purified Cl subcomponents even when HSA was added in 100 fold excess, nor did HSA compete with defensin binding to Ci in NHS or NHP (not shown).…”

Section: Discussionmentioning

confidence: 99%

Identification of defensin binding to C1 complement

et al. 1994

View full text Add to dashboard Cite

In human serum we found strong defensin binding to the complexes of activated Cl complement (CT) and Cl inhibitor (Cli). Purified Clq, activated Cl tetrame_r (T&) and Cli did not bind defensin. When f& was dissociated by EDTA, only the activated Cls (Cls) bound defensin. Binding of defensins to Cl complement represents a newly recognized bridge between the complement-and phagocyte-mediated host defenses, and a potential mechanism for protecting infected tissue from cytotoxic injury by defensin.

show abstract

Section: Discussionmentioning

confidence: 99%

Identification of defensin binding to C1 complement

et al. 1994

View full text Add to dashboard Cite

show abstract

“…This form of ␣ 2 M is fully functional as a proteinase inhibitor but is not recognized by the cell surface receptor, which is an ␣ 2 M receptor/low density lipoprotein receptor-related protein (LRP) (8,14). This receptor is responsible for the rapid plasma clearance of conformationally transformed ␣ 2 M following its reaction with proteinases or small primary amines that modify the ␣ 2 M thiol ester bonds.…”

mentioning

confidence: 99%

“…This raises the possibility that LCAT circulates in plasma in association with ␣ 2 M. Human ␣ 2 M, the largest known proteinase inhibitor (M r ϭ 720,000), is found at high concentrations (2-5 M) in plasma and in extravascular spaces (8,9). It plays a pivotal role in the clearance of proteinases from the circulation and in regulating their activity in fibrinolysis, coagulation, and complement activation (10,11).…”

mentioning

confidence: 99%

Interaction of Lecithin:Cholesterol Acyltransferase (LCAT)·α2-Macroglobulin Complex with Low Density Lipoprotein Receptor-related Protein (LRP)

Krimbou¹,

Marcil²,

Davignon³

et al. 2001

Journal of Biological Chemistry

View full text Add to dashboard Cite

Human lecithin:cholesterol acyltransferase (LCAT) 1 is a 416-amino acid glycoprotein circulating in plasma associated with lipids and apolipoproteins in the high density lipoprotein (HDL) fraction (1). LCAT plays a key role in cholesterol homeostasis by mediating the production of most of the cholesteryl esters in human plasma. It has been suggested (2, 3) that LCAT plays an important role in reverse cholesterol transport (RCT) by creating a concentration gradient for the efflux of free cholesterol from peripheral cells to HDL particles and its conversion to cholesteryl esters. The cholesteryl esters are internalized within the lipoprotein core for ultimate transport to the liver for clearance or recycling. Thus, factors affecting the structure, activity, or concentration of LCAT are likely to affect the homeostasis of plasma cholesterol and the RCT process, one of several proposed mechanisms (4) by which HDL may protect against atherosclerosis. Recent investigations (5) suggest that LCAT can act as an antioxidant and prevent the accumulation of oxidized lipid in plasma lipoproteins. In human plasma, LCAT is almost entirely associated with lipoproteins containing apoA-I, its principal physiological activator (6). Francone et al.(1) have shown the presence of LCAT, cholesteryl ester transfer protein, apoD, and a small amount of apoA-I in a complex termed pre-␤ 3 -LpA-I that is involved in the esterification and transfer of cell-derived cholesterol.We have recently found (7) an association between apoE and ␣ 2-macroglobulin (␣ 2 M) in human plasma, when we observed that LCAT and apoE migrate to the same position in twodimensional electrophoretic gels together with ␣ 2 M, in particles 18.5 nm in diameter. This raises the possibility that LCAT circulates in plasma in association with ␣ 2 M. Human ␣ 2 M, the largest known proteinase inhibitor (M r ϭ 720,000), is found at high concentrations (2-5 M) in plasma and in extravascular spaces (8, 9). It plays a pivotal role in the clearance of proteinases from the circulation and in regulating their activity in fibrinolysis, coagulation, and complement activation (10, 11). ␣ 2 M is also a carrier of specific cytokines and various nonproteolytic proteins that include the transforming growth factor TGF-␤, the platelet-derived growth factor-BB (12), the ␤-amyloid peptide (13), and recently, apolipoprotein E (7).The binding affinities of ␣ 2 M for different non-proteolytic

show abstract

“…Upon interaction of proteinases with ~Ms a large structural rearrangement, known as transformation is initiated by cleavage within the exposed 'bait regions', resulting in entrapment and inhibition of the proteinase (for reviews, see [1,2]). Transformation of c~Ms exposes a previously concealed receptor binding domain, important for the rapid clearance from the circulation [3][4][5].…”

Section: Introductionmentioning

confidence: 99%

Expression and refolding of a high‐affinity receptor binding domain from rat α₁‐macroglobulin

et al. 1995

Self Cite

View full text Add to dashboard Cite

A recombinant version of the receptor binding domain of rat at-macroglobulin (RBDv) consisting of residues 1319-1474 has been expressed in E. coil. Competition experiments with USl-labelled methylamine treated human a2-macroglobulin reveal that the th-macroglobulin-RBDv exhibit the same high affinity for the c~2-macroglobulin receptor as the entire 40 kDa light chain from rat a~-macroglobulin. It is therefore concluded, that all determinants for receptor interaction reside in the C-terminal approx. 150 residues of the t~-macroglobulin subunit.

show abstract

α2-Macroglobulin and Related Thiol Ester Plasma Proteins

Cited by 103 publications

References 662 publications

Identification of defensin binding to C1 complement

Identification of defensin binding to C1 complement

Interaction of Lecithin:Cholesterol Acyltransferase (LCAT)·α2-Macroglobulin Complex with Low Density Lipoprotein Receptor-related Protein (LRP)

Expression and refolding of a high‐affinity receptor binding domain from rat α₁‐macroglobulin

Contact Info

Product

Resources

About

α2-Macroglobulin and Related Thiol Ester Plasma Proteins

Cited by 103 publications

References 662 publications

Identification of defensin binding to C1 complement

Identification of defensin binding to C1 complement

Interaction of Lecithin:Cholesterol Acyltransferase (LCAT)·α2-Macroglobulin Complex with Low Density Lipoprotein Receptor-related Protein (LRP)

Expression and refolding of a high‐affinity receptor binding domain from rat α1‐macroglobulin

Contact Info

Product

Resources

About

Expression and refolding of a high‐affinity receptor binding domain from rat α₁‐macroglobulin