MECHANISMS OF OXIDIZED CHYLOMICRON-INDUCED LEUKOCYTE-ENDOTHELIAL CELL-ADHESION

The objectives of this study were to determine whether oxidatively mod ified chylomicrons (oxCM) can elicit leukocyte-endothelial cell adhesi on in the mesenteric microcirculation and to define the mechanisms und erlying the oxCM-induced adhesive interactions. Oxidation of chylomicr ons (CM) with the peroxyl radical generator 2,2'-azobis(2-amidinopropa ne)hydrochloride was associated with the formation of thiobarbituric a cid-reactive substances and lipid hydroperoxides. Leukocyte rolling, a dherence, and emigration as well as erythrocyte velocity were monitore d in rat mesenteric venules infused with either native CM or oxCM, oxC M, but not native CM, increased the numbers of rolling, adherent, and emigrated leukocytes. The oxCM-induced leukocyte adherence was signifi cantly blunted by pretreating the animals with either superoxide dismu tase, a platelet-activating factor (PAF) receptor antagonist, or monoc lonal antibodies (MAb) directed against either CD11/CD18 or intracellu lar adhesion molecule 1. A MAb against P-selectin reduced oxCM-induced leukocyte rolling but not adherence. These findings suggest that the increased plasma oxCM levels associated with ingestion of oxidized lip ids may promote leukocyte adhesion through a mechanism that involves t he superoxide anion, PAF, and adhesion receptors on leukocytes and end othelial cells.