Method for inhibiting angiogenesis with modified platelet factor- 4 and cleaved platelet factor-4

摘要

The present invention is based of the discovery of two modified forms of human platelet factor-4, herein named MPF-4 and CPF-4, which were isolated from serum free culture medium of lipopolysaccharide- stimulated peripheral blood leukocytes. Amino acid sequence determination revealed that MPF-4 shares homology with platelet factor-4 beginning at N- terminal residue 17. CPF-4 consists of MPF-4 disulfide bonded to the 16 N- terminal residues of platelet factor-4. Both MPF-4 and CPF-4 are potent inhibitors of endothelial cell proliferation, approximately 10-100 fold more potent than native or recombinant platelet factor-4, making them useful in the treatment of angiogenic diseases.