New cell attachment peptide sequences from conserved epitopes in the carboxy termini of fibrinogen.
Fibrinogen seems to contribute significantly to cell binding and recruitment into wounds besides its major role in clot formation. We describe 19- to 21-mer cell-binding (haptotactic) peptides from the C-termini of fibrinogen beta-chain (Cbeta), the extended alphaE chain, and near the C-terminal of the gamma-chain. When these peptides were covalently bound to a biologically inert matrix such as Sepharose beads (SB), they elicited beads attachment to cells, mostly of mesenchymal origin (including fibroblasts, endothelial cells, and smooth muscle cells) as well as some transformed cell lines. Based on such haptotactic activity, these peptides were termed "haptides." By contrast, peptides homologous to fibrinogen C-termini alpha- and gamma-chains elicited no such activity. The haptide Cbeta could not block the interaction of fibroblasts with antibodies directed against integrins beta(1), alpha(v), alpha(v)beta(1), alpha(v)beta(3), and alphaIIbeta(3). Moreover, GRGDS peptide could not inhibit enhanced cell binding to SB-Cbeta, as expected from an integrin-mediated process. In soluble form the haptides were accumulated in cells with nonsaturable kinetics without any toxic or proproliferative effects in concentrations up to 80 microM. These findings suggest that the conserved haptidic sequences within fibrin(ogen) can be associated with the adhesion and migration of cells into fibrin clots and may have a significant role in normal wound healing and in various pathological conditions.
Gorodetsky
Raphael
R
Biotechnology and Radiobiology Laboratory, Sharett Institute of Oncology, Hadassah University Hospital, P.O. Box 12000, 91120, Jerusalem, Israel. Rafi@Hadassah.org.il
Vexler
Akiva
A
Shamir
Meir
M
An
Jianqiang
J
Levdansky
Lilia
L
Shimeliovich
Irina
I
Marx
Gerard
G
D000818:Animals; D001777:Blood Coagulation / Q000502:physiology*; D002417:Cattle; D002448:Cell Adhesion / Q000502:physiology*; D002460:Cell Line; D002633:Chemotaxis / Q000502:physiology; D000939:Epitopes / Q000737:chemistry*; D005057:Eukaryotic Cells / Q000378:metabolism*; D005340:Fibrinogen / Q000737:chemistry*; D006801:Humans; D051379:Mice; D010455:Peptides / Q000737:chemistry*; D017434:Protein Structure, Tertiary / Q000502:physiology; D051381:Rats; D017386:Sequence Homology, Amino Acid; D014945:Wound Healing / Q000502:physiology*
D000939:Epitopes; D010455:Peptides; D005340:Fibrinogen