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Thrombin adhesive properties: Induction by plasmin and heparan sulfate

, : Thrombin adhesive properties: Induction by plasmin and heparan sulfate. Journal of Cell Biology 123(5): 1279-1287

We have previously demonstrated that chemically modified thrombin preparations induce endothelial cell (EC) adhesion, spreading and cytoskeletal reorganization via an Arg-Gly-Asp (RGD) sequence and the alpha v beta 3 integrin. Native thrombin, however, did not exhibit adhesive properties, consistent with crystal structure analysis, showing that Gly-Asp residues of the RGD epitope are buried within the molecule. We have now identified a possible physiological mean of converting thrombin to an adhesive protein. Plasmin, the major end product of the fibrinolytic system, converted thrombin to an adhesive protein for EC in a time and dose-dependent manner. EC adhesion and spreading was also induced by a low molecular weight (approximately 3,000 D) cleavage fragment generated upon incubation of thrombin with plasmin. Cell adhesion mediated by this fragment was completely inhibited by the synthetic peptide GRGDSP. Conversion of thrombin to an adhesive molecule was significantly enhanced in the presence of heparin or heparan sulfate, while other glycosaminoglycans (GAGs) (e.g., dermatan sulfate, keratan sulfate, chondroitin sulfate) had no effect. The role of cell surface heparan sulfate in thrombin conversion to EC adhesive protein was investigated using CHO cell mutants defective in various aspects of GAG synthesis. Incubation of both thrombin and a suboptimal amount of plasmin on the surface of formaldehyde fixed wild-type CHO-KI cells resulted in an efficient conversion of thrombin to an adhesive molecule, as indicated by subsequent induction of EC attachment. In contrast, there was no effect to incubation of thrombin and plasmin with fixed CHO mutant cells lacking both heparan sulfate and chondroitin sulfate, or with cells expressing no heparan sulfate and a three-fold increase in chondroitin sulfate. A similar gain of adhesive properties was obtained upon incubation of thrombin and plasmin in contact with native, but not heparinase-treated extracellular matrix (ECM) produced by cultured ECs. It appears that cell surface and ECM-associated heparan sulfate modulate thrombin adhesive properties through its heparin binding site in a manner that enables suboptimal amounts of plasmin to expose the RGD domain. Our results demonstrate, for the first time, a significant modulation of thrombin molecule by heparin, resulting in its conversion to a potent adhesive protein for ECs. This conversion is most effective in contact with cell surfaces, basement membranes and ECM.


PMID: 8245131

DOI: 10.2307/1616032

Other references

Sugar, I., 1998: Steppe plants in the flora and vegetation of the Dinaric regions of Croatia. The distribution and significance of Carex humilis and Chrysopogon gryllus in the flora and vegetation of the Dinaric Alps of Croatia are discussed.

Kidin V.V.; Sukov A.A.; Mashkina N.G., 1982: Yield and quality of winter rye green mass when ammonium nitrate is applied at different times. Izvestiya Timiryazevskoi Sel'skokhozyaistvennoi Akademii (5): 183-185

Alekperova, N.A., 1961: Discovery of two bones of fossil deer at Lokbatana. Izvestiya Akademii Nauk Azerbaidzhanskoi SSR Geol Geog, 5: 85-94

Erasmus, J.E.; Liebenberg, C.R., 1952: A numerical criterion of conformation in table birds. A regression coefficient on carcass weight is established for each carcass character in question for the whole population, and the mean measurements of the various groups are adjusted accordingly. By eliminating carcass weight it is possible to co...

Alessandrini, A., 1938: Incidence of Brucella Infection in Italy with Special Reference to Arezzo Province. reports that there is not a single region in the whole of Italy which is not affected with undulant fever. The greatest incidence occurs in Sicily, where about 30 % of the population are said to be infected. Br. melitensis is the cause of disease...

Rytz, T., 2002: Political involvement of nurses. The Bern Hospital Movement. Krankenpflege. Soins Infirmiers 93(5): 20-22

Meurer K.P.; Voegtle F., 1986: Helical molecules in organic chemistry. Asami, M , K G Heumann, H J Keller, K P Meurer, T Mukaiyama, Z G Soos And F Voegtle Topics in Current Chemistry, 127 Organic Chemistry Vii+221p Springer-Verlag: Berlin, West Germany; New York, N Y , Usa Illus 1-76, 1985

Connally, N.P.; Yousey-Hindes, K.; Meek, J., 2013: Selection of neighborhood controls for a population-based Lyme disease case-control study by using a commercial marketing database. The selection of controls is an important methodological consideration for case-control studies. Neighborhood-matched control selection is particularly crucial for studies of vector-borne disease, such as Lyme disease, for which risk is intrinsica...

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Metz S.A., 1983: Glucose promotes arachidonic acid turnover and lip oxygenation in rat islets. Clinical Research: 739a