AJP - Lung Cellular and Molecular Physiology, Vol 267, Issue 6 761-L765, Copyright © 1994 by American Physiological Society
Insulin-like growth factor axis in airway smooth muscle cells
J. P. Noveral, A. Bhala, R. L. Hintz, M. M. Grunstein and P. Cohen
Department of Pediatrics, Joseph Stokes, Jr., Research Institute, Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine 19104.
Insulin-like growth factors (IGFs) mediate cell proliferation and
differentiation and bind with high affinities and specificities to IGF
receptors and IGF-binding proteins (IGFBPs). We examined the roles of these
three groups of proteins in cultured rabbit airway smooth muscle (ASM)
cells. Affinity cross-linking of IGF-I and IGF-II to membranes of ASM cells
revealed type 1 and type 2 IGF receptors. Western ligand blot analysis of
ASM cell-conditioned medium revealed the presence of a single IGFBP band
that precipitated with an antibody specific to IGFBP-2. ASM cells secreted
radioimmunoassayable IGF-II; however, no IGF-I was detected under the same
conditions. Two molecular weight forms of IGF-II were produced by the ASM
cells. Exposure of cells to 1,000 ng/ml of IGF-I stimulated them to
proliferate to 230 +/- 9.7% of their respective controls. Exposure to 1,000
ng/ml of IGF-II was approximately 40% as effective as exposure to 1,000
ng/ml of IGF-I. Both IGF-I and IGF-II exhibited binding to the type 1 IGF
receptor. In summary, IGFs are mitogens for cultured rabbit ASM cells, and
their actions are most likely mediated through the type 1 IGF receptor. The
ASM cells secrete IGF-II and IGFBP-2, and the latter could modulate the
actions of the IGFs in these cells.
