Thrombospondin (TSP) forms specific complexes with transforming growth factor-beta (TGF-beta) in the alpha granule releasate of platelets and these TSP-TGF-beta complexes inhibit the growth of bovine aortic endothelial cells (BAE). In these studies, we report that TSP stripped of associated TGF-beta (sTSP) retained growth inhibitory activity which was partially reversed by a neutralizing antibody specific for TGF-beta. Since BAE cells secrete latent TGF-beta, we determined whether sTSP activates the latent TGF-beta secreted by BAE cells. Cells were cultured with or without sTSP and then the conditioned medium was tested for the ability to support TGF-beta-dependent normal rat kidney (NRK) colony formation in soft agar. Medium conditioned with sTSP showed a dose- and time-dependent ability to stimulate BAE-secreted TGF-beta activity, reaching maximal activation by 1-2 h with 0.4 micrograms/ml (0.9 nM) sTSP. The sTSP-mediated stimulation of TGF-beta activity is not dependent on serum factors and is not a general property of extracellular matrix molecules. The sTSP-mediated stimulation of TGF-beta activity was blocked by a mAb specific for sTSP and by neutralizing antibodies to TGF-beta. Activation of BAE cell secreted latent TGF-beta by sTSP can occur in the absence of cells and apparently does not require interactions with cell surface molecules, since in conditioned medium removed from cells and then incubated with sTSP, activation occurs with kinetics and at levels similar to what is seen when sTSP is incubated in the presence of cells. Serine proteases such as plasmin are not involved in sTSP-mediated activation of TGF-beta. Factors that regulate the conversion of latent to active TGF-beta are keys to controlling TGF-beta activity. These data suggest that TSP is a potent physiologic regulator of TGF-beta activation.
Skip Nav Destination
Article navigation
15 August 1993
Article|
August 15 1993
Thrombospondin causes activation of latent transforming growth factor-beta secreted by endothelial cells by a novel mechanism
S Schultz-Cherry,
S Schultz-Cherry
Department of Pathology, University of Alabama, Birmingham 35294-0019.
Search for other works by this author on:
JE Murphy-Ullrich
JE Murphy-Ullrich
Department of Pathology, University of Alabama, Birmingham 35294-0019.
Search for other works by this author on:
S Schultz-Cherry
Department of Pathology, University of Alabama, Birmingham 35294-0019.
JE Murphy-Ullrich
Department of Pathology, University of Alabama, Birmingham 35294-0019.
Online ISSN: 1540-8140
Print ISSN: 0021-9525
J Cell Biol (1993) 122 (4): 923–932.
Connected Content
Corrected article
Correction
Citation
S Schultz-Cherry, JE Murphy-Ullrich; Thrombospondin causes activation of latent transforming growth factor-beta secreted by endothelial cells by a novel mechanism. J Cell Biol 15 August 1993; 122 (4): 923–932. doi: https://doi.org/10.1083/jcb.122.4.923
Download citation file:
Sign in
Don't already have an account? Register
Client Account
You could not be signed in. Please check your email address / username and password and try again.
Could not validate captcha. Please try again.
Sign in via your Institution
Sign in via your InstitutionEmail alerts
Connected Content
Advertisement
Advertisement