Role of mast cells in oxidized low-density lipoprotein-induced microvascular dysfunction

The American Journal of Physiology
L Liao, D N Granger

Abstract

Previous studies demonstrated that human low-density lipoprotein (LDL) oxidized with Cu2+ 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, fluorescein isothiocyanate-albumin leakage, and mast cell degranulation were monitored in rat mesentery before and during local intra-arterial infusion of either normal LDL (nLDL) or copper-oxidized LDL (CuLDL). Infusion of CuLDL, but not nLDL, 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 iodoxamide significantly reduced CuLDL-induced mast cell degranulation. The mast cell stabilization was accompanied by attenuated leukocyte-endothelial cell adhesion and albumin leakage responses to CuLDL. The results of this study indicate that 1) CuLDL-induced microvascular dysfunction (albumin leakage) involves the activation of mast cells, and ...Continue Reading

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