Background: The normal response to tissue injury involves a complex sequence of inflammation and repair of epithelial and mesenchymal structures through a coordinated process of chemotaxis and cellular proliferation directed by specific chemical mediators. One mediator that is probably important to these processes is basic fibroblast growth factor (bFGF), a polypeptide present in diverse tissues and a potent chemotactic, mitogenic, and angiogenic factor in vitro. Although many cells have receptors for bFGF, the precise role of this factor as a paracrine mediator in vivo remains disputable because a mechanism for its secretion has not been elucidated. bFGF is known to be capable of binding to heparin, and our data demonstrate bFGF in mast cells (MCs) that also produce many other mediators (including heparin) important for wound healing and angiogenesis.
Experimental design: We used nucleic acid in situ hybridization to detect bFGF-specific mRNA transcripts within MCs in formalin-fixed, paraffin-embedded specimens of nonlesional human skin and skin containing increased numbers of MCs, including granulation tissues, benign cutaneous mastocytosis, and solitary neurofibromas. Immunohistochemistry was used to confirm bFGF protein expression in each tissue studied.
Results: All tissues examined contained MCs that expressed bFGF mRNA transcripts. bFGF protein was also detected in MCs, but the intensity of labeling was dependent on prior treatment of the tissues with heparinase, suggesting that epitopes recognized by the bFGF-specific antiserum were masked by endogenous heparin.
Conclusions: The results further elucidate the mechanism of involvement of MCs in tissue repair and angiogenesis and suggest that bFGF produced by MCs is bound to intracellular heparin. Thus, it seems possible that release of heparin by degranulation from MCs also may result in the release of biologically active bFGF in vivo.