ABSTRACT
Within tissues, regulation of the biological effects of growth factor activity is dominated by mechanisms other than growth factor expression and receptor binding (1). While some growth factors, EGF and TGF-a for example, are synthesized as large precursors that remain bound to cell membranes where they are active as nondiffusible transmembrane species, others are secreted. However, growth factors that are secreted are no longer considered to be dif fusible factors active in solution, but bound by components of extracellular and pericellular matrices. It is these interactions that determine the net activity and specific extracellular location of the secreted growth factors. Thus, the extracellular matrix plays a major role in the control of growth factor-medi ated signaling, cell proliferation, and differentiation (2). A number of proteo glycans and proteins present within the extracellular matrix of bronchial tissue are known to bind growth factors that are considered to contribute to the patho-
genesis of asthma, such as TGF-(3, FGF-2, IGFs, PDGF, HB-EGF, and VEGF (3). Such binding influences not only the distribution of growth factors, but their potency, diffusion properties, and stability. Release of preformed growth factors from storage sites in the extracellular matrix or activation of latent complexes provides a means of rapid intercellular signaling, which is indepen dent of de novo synthesis of the growth factors. Initiation of activation of these growth factors is therefore a posttranslational, extracellular process that depends on their release from inactive matrix-bound complexes.
