Abstract: The in vivo role of the N-terminal lectin-like domain of thrombomodulin was studied by using homologous recombination in murine ES cells to create mutant mice that lack this region of thrombomodulin. Phenotypic analysis shows that said mice respond identically to their wild type littermates following pro-coagulant challenges meaning that the protein C pathway is not altered by the mutation. However, following several inflammatory stimuli, it was observed that the mutant mice showed an elevated neutrophil extravasation in several organs. It is found that leukocyte adhesion could be abrogated by addition of recombinant lectin-domain meaning that said domain has direct anti-inflammatory properties which means that the lectin-like domain can be used to manufacture a medicament useful for the treatment of a variety of inflammatory disease processes.

Abstract: Nucleic acid constructs comprising procoagulant gene sequences under the control of a megakaryocyte-specific promoter are provided. The sequences preferably also comprise a secretory granule sorting domain Also provided are vectors comprising the sequences and methods of gene therapy comprising the use of the various constructs.