Endothelial gaps: time course of formation and closure in inflamed
venules of rats.
Baluk, Peter, Akira Hirata, Gavin Thurston, Takashi Fujiwara[acute]a,
Chris R. Neal, C. Charles Michel, and Donald M. McDonald.
Cardiovascular Research Institute and Department of Anatomy,
University of California, San Francisco, CA 94143, USA and
Departments of Anatomy and Ophthalmology, Kumamoto University School
of Medicine, Kumamoto 860, JAPAN and [acute]aLaboratory Animal
Center, Ehime University School of Medicine, Shigenobu, Ehime 791-02,
JAPAN and Department of Physiology and Biophysics, St. Mary's
Hospital Medical School, Imperial College of Science, Technology and
Medicine, Norfolk Place, London W2 1PG, UK
APStracts 3:0170L, 1996.
In the rat trachea, substance P causes rapid but transient plasma
leakage. We sought to determine how closely the number, morphology,
and size of endothelial gaps correspond to the time course of this
leakage. Endothelial gaps were examined by scanning electron
microscopy (EM), transmission EM, or by light microscopy after silver
nitrate staining. Substance P-induced leakage of the particulate
tracer Monastral blue peaked at 1 min, but decreased with a half-life
of 0.3 min. The number of silver-stained gaps also peaked at 1 min
then decreased significantly more slowly (half-life, 1.9 min) than
the leakage. Scanning EM revealed two types of endothelial gaps,
designated vertical gaps and oblique slits. Vertical gaps
predominated at peak leakage, while oblique slits became more common
as the leakage diminished. Measurements of the mean diameter of
vertical gaps made by light microscopy, scanning EM, and transmission
EM were all in the range of 0.36 to 0.47 m. Fingerlike endothelial
cell processes that appeared during gap formation became shorter as
the leakage diminished (mean length: 1.44 m at 1 min compared to 1.06
m at 3 min after substance P), suggesting a role in gap closure. We
conclude that the plasma leakage occurring immediately after an
inflammatory stimulus results from the rapid formation of endothelial
gaps. Multiple factors including alterations in gap morphology, gap
closure, and changes in driving force are likely to participate in
the rapid decrease in the leakage.
Received 17 June 1996; accepted in final form 11 September 1996.
APS Manuscript Number L183-6.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 5 November 1996