Human alpha 2-macroglobulin (alpha 2M) is a proteinase inhibitor and carrier of certain growth factors, including transforming growth factor beta 1 (TGF-beta 1). The constitutively synthesized homologue of human alpha 2M in the adult rat is alpha 1M. Rat alpha 2M is an acute-phase reactant, expressed at high levels in experimental trauma, pregnancy and in certain pathological conditions. The physiological role of rat alpha 2M is not known. In this investigation, we demonstrated that rat alpha 1M and rat alpha 2M bind TGF-beta 1. The equilibrium dissociation constants (KD) for the binding of TGF-beta 1 to the native forms of alpha 1M and alpha 2M were 257 and 109 nM respectively. alpha 1M underwent conformational change when it reacted with methylamine. The resulting product bound TGF-beta 1 with higher affinity (32 nM). Methylamine-treated rat alpha 2M did not undergo conformational change and did not bind TGF-beta 1 with increased affinity. Previous studies suggest that the native conformation may be the principal form responsible for the cytokine-carrier activity of alpha 2M in plasma and serum-supplemented cell culture medium. To confirm that native rat alpha 2M is a more efficient TGF-beta 1 carrier than native alpha 1M, fetal bovine heart endothelial cell (FBHE) proliferation assays were performed. TGF-beta 1 (5 pM) inhibited FBHE proliferation, and native alpha 2M (0.3 microM) counteracted this activity whereas alpha 1M (0.3 microM) had almost no effect. Rat alpha 2M underwent conformational change when it reacted with plasmin incorporating 1.1 mol of plasmin/mol. alpha 2M-plasmin bound TGF-beta 1; the KD (61 nM) was lower (P < 0.01) than that determined for the native alpha 2M-TGF-beta 1 interaction. These studies demonstrate that both rat alpha-macroglobulins are carriers of TGF-beta 1. The native form of rat alpha 2M probably has a predominant role, compared with native alpha 1M, as a TGF-beta 1 carrier in the plasma during the acute-phase response.
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December 1995
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Research Article|
December 01 1995
Differences in the binding of transforming growth factor β1 to the acute-phase reactant and constitutively synthesized α-macroglobulins of rat
D J Webb;
D J Webb
1Departments of Charlottesville, VA 22908, U.S.A.
*Biochemistry, Charlottesville, VA 22908, U.S.A.
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K P Crookston;
K P Crookston
1Departments of Charlottesville, VA 22908, U.S.A.
*Biochemistry, Charlottesville, VA 22908, U.S.A.
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N L Figler;
N L Figler
1Departments of Charlottesville, VA 22908, U.S.A.
†Pathology, University of Virginia Health Sciences Center, Charlottesville, VA 22908, U.S.A.
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J Lamarre;
J Lamarre
1Departments of Charlottesville, VA 22908, U.S.A.
‡Department of Biomedical Sciences, University of Guelph, Guelph, Ontario, Canada NiG2W1
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S L Gonias
S L Gonias
1Departments of Charlottesville, VA 22908, U.S.A.
*Biochemistry, Charlottesville, VA 22908, U.S.A.
†Pathology, University of Virginia Health Sciences Center, Charlottesville, VA 22908, U.S.A.
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Publisher: Portland Press Ltd
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© 1995 The Biochemical Society, London
1995
Biochem J (1995) 312 (2): 579–586.
Citation
D J Webb, K P Crookston, N L Figler, J Lamarre, S L Gonias; Differences in the binding of transforming growth factor β1 to the acute-phase reactant and constitutively synthesized α-macroglobulins of rat. Biochem J 1 December 1995; 312 (2): 579–586. doi: https://doi.org/10.1042/bj3120579
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