Motogenic effect of nitric oxide: nitric oxide is necessary for a switch from stationary to locomoting phenotype in epithelial cells. Noiri, Eisei, Tatyana Peresleni, Neil Srivastava, Pamela Weber, Wadie F. Bahou, Natalia Peunova, and Michael S. Goligorsky. Departments of Medicine, Physiology and Biophysics, and Ophthalmology, State University of New York at Stony Brook, NY 11794, and Cold Spring Harbor Laboratory, NY 11724
APStracts 2:0335C, 1995.
The restitution of epithelial integrity is accomplished in part by cell migration. Studying this process, we have found that nitric oxide release from migrating epithelial BSC-1 cells displayed a biphasic response to the inflicted wounds: an initial transient release of nitric oxide is followed by a delayed sustained elevation. While the constitutive endothelial NO synthase (ecNOS) did not show any spatial or temporal changes associated with wounding, the inducible NO synthase (iNOS) became expressed 3 h after wounding and showed higher abundance at the edges of epithelial wounds. L-arginine (L-Arg) or NO-donor, SNAP, exerted motogenic effect in epithelial, as well as in endothelial cells. Inhibition of NOS with NG-nitro L -arginine methyl ester (L-NAME) or a selective knock-out of iNOS with antisense oligodeoxynucleotides reduced the rate of spontaneous or EGF-induced BSC-1 cell migration. Migrating cells showed by the polarized expression of NOS, suggesting a head-to-rear NO gradient. Several growth factors (EGF, IGF-I, HGF, b-FGF) were motogenic for BSC-1 cells, but this effect was abrogated by pretreatment with L -NAME. We conclude that endogenous NO production is a prerequisite for BSC-1 cell migration. A vectorial NO release may be essential for the spatially and temporally coordinated reciprocal phenomena occurring at the leading and trailing edge of locomoting epithelial cells. Although the exact mode of NO action remains uncertain, it is conceivable that the production of NO serves as a cellular switch from the stationary to the locomoting epithelial phenotype. 

Received 2 June 1995; accepted in final form 1 September 1995.
APS Manuscript Number C310-5.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 23 September 1995.