Role of mast cells in oxidized low density lipoprotein-induced microvascular dysfunction. Liao, Lianxi, and D. Neil Granger. Department of Physiology and Biophysics, Louisiana State University Medical Center, Shreveport, Louisiana 71130
APStracts 3:0164H, 1996.
Previous studies have demonstrated that human low-density lipoprotein (LDL) oxidized with Cu++ promotes leukocyte-endothelial cell adhesion, mast cell degranulation and albumin extravasation in rat mesentery. The objective of this study was to determine whether the mast cell degranulation elicited by oxidized LDL accounts for the accompanying microvascular responses. Leukocyte rolling, adherence, and emigration, FITC-albumin leakage, and mast cell degranulation were monitored in rat mesentery prior to and during local intra -arterial infusion of either normal LDL (n-LDL) or copper oxidized LDL (Cu-LDL). Infusion of Cu-LDL, but not n-LDL, elicited significant increases in leukocyte rolling, adherence and emigration, albumin leakage and mast cell degranulation. Pretreatment with the mast cell stabilizing agent ketotifen or superfusion of the mesenteric microcirculation with lodoxamide significantly reduced Cu-LDL-induced mast cell degranulation. The mast cell stabilization was accompanied by attenuated leukocyte-endothelial cell adhesion and albumin leakage responses to Cu-LDL. The results of this study indicate that 1) Cu -LDL-induced microvascular dysfunction (albumin leakage) involves the activation of mast cells, and 2) the protective action of mast cell stabilizers may be related to their ability to blunt Cu-LDL-induced leukocyte-endothelial cell interactions in postcapillary venules. 

Received 2 February 1996; accepted in final form 10 April 1996.
APS Manuscript Number H106-6.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 1 May 96