The role of putative fibrinogen Aalpha-, Bbeta-, and GammaA-chain integrin binding sites in endothelial cell-mediated clot retraction.
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 Aalpha-chain RGD residues at 572-574 or lacking the gamma-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 alphavbeta3 partially inhibited the endothelial cell-mediated retraction of clots formed from plasma fibrinogen. As expected, an antibody to the platelet integrin alphaIIbbeta3 did not inhibit endothelial cell-mediated clot retraction. These results indicate that this retraction is mediated at least in part by alphavbeta3. These results support the conclusion that (a) 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.
Smith
R A
RA
University of Memphis, Department of Microbiology and Molecular Cell Sciences, Memphis, Tennessee 38152, USA. rsmith@utmem1.utmem.edu
Mosesson
M W
MW
Rooney
M M
MM
Lord
S T
ST
Daniels
A U
AU
Gartner
T K
TK
D001665:Binding Sites; D002478:Cells, Cultured; D003018:Clot Retraction; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D005340:Fibrinogen / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D019030:Receptors, Vitronectin / Q000378:metabolism
D005338:Fibrin Fibrinogen Degradation Products; D016023:Integrins; D019030:Receptors, Vitronectin; D005340:Fibrinogen