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J. Biol. Chem., Vol. 280, Issue 42, 35490-35498, October 21, 2005

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Fibrin but Not Adsorbed Fibrinogen Supports Fibronectin Assembly by Spread Platelets

EFFECTS OF THE INTERACTION OF IIb3 WITH THE C TERMINUS OF THE FIBRINOGEN -CHAIN^*

Jaehyung Cho, Jay L. Degen, Barry S. Coller¶, and Deane F. Mosher1

From the Molecular and Cellular Pharmacology Program and Department of Medicine, University of Wisconsin-Madison School of Medicine, Madison, Wisconsin 53706, Children's Hospital Research Foundation, University of Cincinnati College of Medicine, Cincinnati, Ohio 45229, and ^¶Laboratory of Blood and Vascular Biology, The Rockefeller University, New York, New York 10021

We investigated the assembly of soluble fibronectin by lysophosphatidic acid-activated platelets adherent to fibrinogen or fibrin. More fibronectin was assembled by activated platelets spread on fibrin matrices than by platelets spread on adsorbed fibrinogen. The difference between platelets adherent to fibrinogen and fibrin occurred under both static and flow conditions. Similar differences were seen in binding of the 70-kDa N-terminal fragment of fibronectin that recognizes fibronectin assembly sites on adherent cells. Antibody and peptide blocking studies demonstrated that IIb3 integrin mediates platelet adhesion to fibrinogen, whereas both v3 and IIb3 mediate platelet adhesion to fibrin. The hypothesis that engagement of the C-terminal QAGDV sequence of the fibrinogen -chain by IIb3 inhibits the ability of the platelet to assemble fibronectin was tested by several experiments. Activated platelets adherent to adsorbed mutant fibrinogen lacking the QAGDV sequence (5FG) were assembly-competent, as were platelets adherent to adsorbed normal fibrinogen that had been pretreated with the 7E9 antibody to the C terminus of the -chain. Moreover, adsorbed normal fibrinogen but not 5FG suppressed the ability of co-adsorbed fibronectin to direct assembly of soluble fibronectin by spread platelets. The suppressive effect was lost when a surface of co-adsorbed fibronectin and fibrinogen was pretreated with 7E9. These results support a model in which the engagement of IIb3 by the C-terminal sequence of the fibrinogen -chain initiates signals that suppress subsequent fibronectin assembly by spread platelets. This interaction is less dominant when platelets adhere to fibrin, resulting in enhanced fibronectin assembly.

Received for publication, June 9, 2005 , and in revised form, July 13, 2005.

^* The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental material.

¹ To whom correspondence should be addressed: Dept. of Medicine, University of Wisconsin-Madison, 4285 Medical Sciences Center, 1300 University Ave., Madison, WI 53706 Tel.: 608-262-1576; Fax: 608-263-4969; E-mail: dfmosher{at}wisc.edu.

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