Ultrastructural immunolocalization of basic fibroblast growth factor in endothelial cells: morphologic evidence for unconventional secretion of a novel protein.

Basic fibroblast growth factor (bFGF) is one of the most potent angiogenic factors. Unlike many other growth factors, bFGF lacks a classic peptide sequence for its secretion. Recent studies suggest that there is an unconventional secretory pathway for this growth factor. The aim of this study was to identify the specific location of bFGF in endothelial cells and to find morphologic evidences concerning its synthesis, storage and release from endothelial cells. The capillaries in hippocampus, adrenal gland, kidney, peripheral nerves as well as the vessels in connective tissues were analysed by using immunogold labeling techniques at electron microscope level. Results show that endogenous bFGF is mainly located in the nuclei of endothelial cells. Slight immunoreactivity is found in the cytoplasm. Immunolabeling is notably absent in pinocytotic vesicles, Golgi complexes, endoplasmic reticulum, nuclear membrane and intercellular junctions. These results provide morphologic evidence suggesting that endothelial cells might export bFGF via unique cellular pathways that are clearly distinct from classical signal peptide mediated secretion and/or release of this protein could be directly through mechanically induced disruptions of these cells. The current study support the recent hypothesis related with unconventional secretory pathway for bFGF as some other "cargo" proteins.