Leukocyte adhesion and microvessel permeability.
He, P., J. Wang, and M. Zeng.
Department of Human Physiology, School of Medicine, University of California,
Davis, California 95616
APStracts 7:0072H, 2000.
To investigate the direct effect of leukocyte adherence to microvessel walls on
microvessel permeability, we developed a method to measure changes in hydraulic
conductivity (Lp) before and after leukocyte adhesion in individually perfused venular
microvessels in frog mesentery. In 19 microvessels that were initially free of leukocyte
sticking or rolling along the vessel wall, control Lp was measured first with Ringer-
albumin perfusate. Blood flow was then restored in each vessel with a reduced flow rate
at the range of 30-116 mum/s to facilitate leukocyte adhesion. Each vessel was
recannulated in 45 min. The mean number of leukocytes adhering to the vessel wall was
237 ± 22 leukocytes/mm2. At the same time, Lp increased to 4.7 ± 0.5 times the control
value. Superfusion of isoproterenol (10 muM) after leukocyte adhesion brought the
increased Lp back to 1.1 ± 0.2 times control in 5-10 min (n = 9). Superfusing
isoproterenol before leukocyte adhesion prevented the increase in Lp (n = 6). However,
the number of leukocytes adhering to the vessel wall was not significantly affected. These
results demonstrated that leukocyte adhesion caused an increase in microvessel
permeability that could be prevented or restored by increasing cAMP levels in endothelial
cells using isoproterenol. Thus cAMP-dependent mechanisms that regulate inflammatory
agent-induced increases in permeability also modulate leukocyte adhesion-induced
increases in permeability but act independently of mechanisms that regulate leukocyte
adhesion to the microvessel wall. Application of ketotifen, a mast cell stabilizer, and
desferrioxamine mesylate, an iron-chelating reagent, attenuated the increase in Lp
induced by leukocyte adhesion, suggesting the involvement of oxidants and the activation
of mast cells in leukocyte adhesion-induced permeability increase. Furthermore, with the
use of a silver staining in vivo technique, the locations of the adherent leukocytes on the
microvessel wall were identified quantitatively in intact microvessels.
Received 25 May 1999; accepted in final form 17 November 1999.
APS Manuscript Number H472-9.
Article publication pending Am J Physiol Heart Circ Physiol
ISSN 1080-4757 Copyright 2000 The American Physiological Society.
Published in APStracts on 29 February 2000