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By recruiting leucocytes to malignant, inflammatory and ischaemic tissues, chemokines significantly affect pathological angiogenesis. g. g. PF-4, MIG, IP-10, ITAC, BCA-1, SLC/6Ckine). Leucocytes and vascular cells influence each other in several ways. First, most leucocytes release numerous angiogenic factors. Mast cells in the skin and mucosa, on the outlook for allergens and pathogens, cause vasodilatation, microvascular leakage and oedema through release of histamine, VEGF and lipid metabolites and coordinate the recruitment of other leucocytes.

12] VEGFA occurs in different isoforms that are encoded by mRNA splice variants derived from a single gene. In the human, at least five different isoforms exist: VEGF121, VEGF145, VEGF165, VEGF189 and VEGF206. These isoforms differ primarily in heparin binding which may affect their diffusion rates in the extracellular space. [3] These proteins interact with three major tyrosine kinases: VEGFR-1 (Flt-1), VEGFR-2 (Flk-1/KDR) and VEGFR-3 and two non-receptor tyrosine kinases; neuropilin 1 and neuropilin 2 that also bind to other ligands.

Tumour Biol 2002;23:185-92. [85] Miao RQ, Agata J, Chao L, Chao J. Kallistatin is a new inhibitor of angiogenesis and tumor growth. Blood 2002;100:3245-52. [86] Bergers G, Brekken R, McMahon G et al. Matrix metalloproteinase-9 triggers the angiogenic switch during carcinogenesis. Nat Cell Biol 2000;2:737-44. [87] Hynes RO. A reevaluation of integrins as regulators of angiogenesis. Nat Med 2002;8:918-21. [88] Hood JD, Cheresh DA. Role of integrins in cell invasion and migration. Nat Rev Cancer 2002;2:91-100.

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