Am. J. Respir. Cell Mol. Biol., Vol 15, No. 5, 11 1996, 590-599.
Enhanced growth response of airway smooth muscle in inbred rats with airway hyperresponsiveness
ME Zacour and JG Martin
Meakins-Christie Laboratories, Royal Victoria Hospital, McGill University, Montreal, Quebec, Canada.
The highly inbred Fisher rat strain demonstrates both hyperresponsiveness
of the airways to bronchoconstrictors and increased amounts of airway
smooth muscle when compared with Lewis rats. We postulated that the excess
airway smooth muscle in Fisher was attributable to a greater sensitivity to
endogenous mitogenic stimuli with signaling mechanisms common to
contractile stimuli. To test this possibility we investigated differences
in the growth response of cultured airway smooth muscle cells (SMC) from
these two strains. The Fisher SMC demonstrated an enhanced growth response
to fetal bovine serum (FBS), as measured both by cell counting and
[3H]thymidine incorporation. The difference in growth response was
attributable to a more rapid transition in Fisher than Lewis SMC from the
G0/G1 phase to the S phase of the cell cycle. When SMC growth was
stimulated by either serotonin, endothelin 1, insulin, platelet-derived
growth factor (PDGF), or combinations of the above factors, significant
interstrain growth response differences were found only with either human
PDGF (AB) or a combination of porcine PDGF (BB) and insulin. A polyclonal
antibody to PDGF was less inhibitory to Fisher than Lewis SMC following
stimulation with FBS. Thus, interstrain growth differences may reflect
different responses to PDGF present in FBS, or to other factors which exert
an influence during the G0 or G1 phase of the cell cycle.
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Copyright © 1996 American Thoracic Society.
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