title: Ultrastructural immunolocalization of basic fibroblast growth factor in mast cell secretory granules. Morphological evidence for bfgf release through degranulation.
abstract: We previously reported that mast cells (MCs) serve as a source of basic fibroblast growth factor (bFGF), a potent angiogenic and mitogenic polypeptide, suggesting that bFGF may mediate MC-related neovascularization and fibroproliferation. Unlike many other growth factors, bFGF lacks a classic peptide sequence for its secretion, and the mechanism(s) for its release remains controversial. Because MCs release a wide spectrum of bioactive products via degranulation, we hypothesized that MC degranulation may be a mechanism of bFGF release and used ultrastructural immunohistochemistry to test the hypothesis. We reasoned that if bFGF is released through degranulation, it should be localized to MC secretory granules. Human tissues with chronic inflammation and rat/mouse tissues with anaphylaxis were studied. In all tissue samples examined, positive staining (or immunogold particle localization) for bFGF in MCs was predominantly in the cytoplasmic granules. Moderate bFGF immunoreactivity was also found in the nucleus, whereas the cytosol and other subcellular organelles exhibited minimal immunogold particle localization. In contrast, no immunogold particle localization for bFGF was observed in lymphocytes or plasma cells. In rat/mouse lingual tissue undergoing anaphylaxis, immunogold particle localization for bFGF was found not only in swollen cytoplasmic granules but also in the extruded granules of MCs. Three different anti-bFGF antibodies gave similar immunogold particle localization patterns, whereas all controls were negative. These results provide morphological evidence suggesting that, despite the lack of a classic secretory peptide in its structure, bFGF is localized to the secretory granules in MCs and may be released through degranulation.
authors.affiliation: Oregon Health Sciences University, Casey Eye Institute, Portland, Oregon, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Qu
authors.forename: R J
authors.initials: RJ
authors.lastname: Kayton
authors.forename: P
authors.initials: P
authors.lastname: Ahmadi
authors.forename: J M
authors.initials: JM
authors.lastname: Liebler
authors.forename: M R
authors.initials: MR
authors.lastname: Powers
authors.forename: S R
authors.initials: SR
authors.lastname: Planck
authors.forename: J T
authors.initials: JT
authors.lastname: Rosenbaum
mesh_terms: D000818:Animals; D003594:Cytoplasmic Granules / Q000737:chemistry*; D016222:Fibroblast Growth Factor 2 / Q000032:analysis* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008407:Mast Cells / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure; D051379:Mice; D008854:Microscopy, Electron; D051381:Rats; D014018:Tissue Distribution
chemical_list: D016222:Fibroblast Growth Factor 2