THE CHICKEN CHEMOTACTIC AND ANGIOGENIC FACTOR (9E3 GENE PRODUCT): ITS ANGIOGENIC PROPERTIES RESIDE IN THE C-TERMINUS OF THE MOLECULE

Abstract

Chicken chemotactic and angiogenic factor (cCAF) is a 9 kDa protein that belongs to the C–X–C family of chemokines and shows high homology to IL-8 and MGSA/groα. It is produced abundantly shortly after wounding and in the granulation tissues of wounds, especially in areas of neovascularization, suggesting that it is important in angiogenesis. In the chorioallantoic membrane (CAM)in vivoassay system, cCAF is chemotactic for monocyte/macrophages and lymphocytes, is angiogenic, and can by itself trigger the formation of granulation-like tissue. We have further investigated the angiogenic properties of this protein to determine what part of the molecule is responsible for this function. Through pellet-release studies in the CAM we show that low doses of the C-terminal 28-aa peptide stimulate oriented blood vessel growth in the CAM without attracting leukocytes. At higher doses the peptide stimulated extensive tortuosity and sprouting of the tertiary blood vessels. Deposition of the peptide under the skin of the wings of newly-hatched chicks resulted in an increase of the number of microvessels in the tissue in the area of application without the presence of leukocytes. Therefore, the C-terminal peptide recapitulates all of the angiogenic properties of the full cCAF molecule, but does not have the chemotactic properties for leukocytes, and it does not cause development of granulation-like tissue. These results coupled with our earlier work in wounded chicks suggest that cCAF directly participates in angiogenesis and that the C-terminal portion of the molecule can perform this function.