The role of putative fibrinogen Aα-, Bβ-, and γA-chain integrin binding sites in endothelial cell-mediated clot retraction

Richard Smith, M. W. Mosesson, Michael M. Rooney, Susan T. Lord, A. U. Daniels, T. Kent Gartner

Research output: Contribution to journalArticle

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Abstract

In this study, endothelial cell-mediated clot retraction was supported by fibrin generated from several purified fractions of plasma fibrinogen, purified proteolytic fragments of plasma fibrinogen, recombinant normal fibrinogen, and recombinant variant fibrinogen. These results were surprising because some of these fibrinogens lack domains that are known binding sites for the integrin receptors that support clot retraction. Specifically, fibrinogens lacking Aα-chain RGD residues at 572-574 or lacking the γ- chain residues AGDV 408-411 supported endothelial cell-mediated clot retraction as well as intact fibrinogen. Thus, clot retraction mediated by endothelial cells is not dependent on either of these sites. A variety of monoclonal antibodies against the integrin α(v)β3 partially inhibited the endothelial cell-mediated retraction of clots formed from plasma fibrinogen. As expected, an antibody to the platelet integrin α(IIb)β3 did not inhibit endothelial cell-mediated clot retraction. These results indicate that this retraction is mediated at least in part by α(v)β3. These results support the conclusion that (α) neither of the two fibrinogen cell binding sites described above is required to support clot retraction or that (b) either site alone or in conjunction with other fibrin(ogen) region(s) can support clot retraction. Thus, endothelial cell-mediated clot retraction appears to be dependent on fibrinogen cell binding sites other than those required to support adhesion of resting platelets to immobilized fibrinogen and platelet aggregation.

Original languageEnglish (US)
Pages (from-to)22080-22085
Number of pages6
JournalJournal of Biological Chemistry
Volume272
Issue number35
DOIs
StatePublished - Aug 29 1997

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Clot Retraction
Endothelial cells
Integrins
Fibrinogen
Endothelial Cells
Binding Sites
Platelets
Fibrin
Plasmas
Blood Platelets
Platelet Aggregation

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

The role of putative fibrinogen Aα-, Bβ-, and γA-chain integrin binding sites in endothelial cell-mediated clot retraction. / Smith, Richard; Mosesson, M. W.; Rooney, Michael M.; Lord, Susan T.; Daniels, A. U.; Gartner, T. Kent.

In: Journal of Biological Chemistry, Vol. 272, No. 35, 29.08.1997, p. 22080-22085.

Research output: Contribution to journalArticle

Smith, Richard ; Mosesson, M. W. ; Rooney, Michael M. ; Lord, Susan T. ; Daniels, A. U. ; Gartner, T. Kent. / The role of putative fibrinogen Aα-, Bβ-, and γA-chain integrin binding sites in endothelial cell-mediated clot retraction. In: Journal of Biological Chemistry. 1997 ; Vol. 272, No. 35. pp. 22080-22085.
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