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Immunocytochemical localization of latent transforming growth factor-beta1 activation by stimulated macrophagesTransforming growth factor-beta1 (TGF-beta) is secreted in a latent form consisting of mature TGF-beta noncovalently associated with its amino-terminal propeptide, which is called latency associated peptide (LAP). Biological activity depends upon the release of TGF-beta from the latent complex following extracellular activation, which appears to be the key regulatory mechanism controlling TGF-beta action. We have identified two events associated with latent TGF-beta (LTGF-beta) activation in vivo: increased immunoreactivity of certain antibodies that specifically detect TGF-beta concomitant with decreased immunoreactivity of antibodies to LAP. Macrophages stimulated in vitro with interferon-gamma and lipopolysaccharide reportedly activate LTGF-beta via cell membrane-bound protease activity. We show through dual immunostaining of paraformaldehyde-fixed macrophages that such physiological TGF-beta activation is accompanied by a loss of LAP immunoreactivity with concomitant revelation of TGF-beta epitopes. The induction of TGF-beta immunoreactivity colocalized with immunoreactive betaglycan/RIII in activated macrophages, suggesting that LTGF-beta activation occurs on the cell surface. Confocal microscopy of metabolically active macrophages incubated with antibodies to TGF-beta and betaglycan/RIII prior to fixation supported the localization of activation to the cell surface. The ability to specifically detect and localize LTGF-beta activation provides an important tool for studies of its regulation.
Document ID
20040142078
Acquisition Source
Legacy CDMS
Document Type
Reprint (Version printed in journal)
Authors
Chong, H.
(Lawrence Berkeley National Laboratory, University of California Berkeley 94720, United States)
Vodovotz, Y.
Cox, G. W.
Barcellos-Hoff, M. H.
Chatterjee, A.
Date Acquired
August 22, 2013
Publication Date
March 1, 1999
Publication Information
Publication: Journal of cellular physiology
Volume: 178
Issue: 3
ISSN: 0021-9541
Subject Category
Life Sciences (General)
Distribution Limits
Public
Copyright
Other
Keywords
NASA Discipline Radiation Health
Non-NASA Center

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