Endothelial cell regulation of polymorphonuclear leukocyte motility and diapedesis in vitro
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Abstract
Polymorphonuclear leukocyte (PMN) migration across endothelial cell (EC) monolayers cultured on acellular amnionic membrane was used as an 1n vitro approximation of diapedesis, to examine the direct influence of confluent endothelial monolayers on PMN motility. PMN random motility and chemotaxis across polycarbonate filters were also studied to determine the influence of EC-derived metabolites and other exogenously applied agents. ECs were aeen to regulate PMN diapedesis and motility by two means. One, by altering intracellular microfilament arrays, ECs increase or decrease monolayer junctional integrity, and thereby present a variable barrier to PMN diapedesis as well as macromolecular permeability. Microfilament arrangements are altered by the vasoactive amines histamine, norepinephrine, and serotonin, by the eicosanoids thromboxane (Tx) ~ and the stable metabolite of prostacyclin, 6-keto-PGFJa • and by the fungal metabolites cytochalasin B and phalloidin. Two, ECs release metabolites that directly influence PKN motility. TxB 2 and an unidentified lipoxygenase product increase PMN diapedesis, random motility, and chemotaxis, and act as chemoattractants. 6-Keto-PGF la increases or decreases diapedesis and chemotaxis depending on its concentration. Release of EC eicosanoids is substrate modulated, with a greater release induced by extracellular matrices as compared to gelatin or plastic aubstrates. These two EC-baaed regulations of PHN motility are interrelated, as vasoactive amines also modulate EC eicosanoid production, and eicosanoids alter EC cytoskeletal patterns and therefore permeability. Both of the EC-based regulations of PMN motility are similarly manipulated by exogenous agents such as amines, arachidonic acid, or arachidonic acid metabolism inhibitors. It is concluded that ECs influence PKN motility and diapedesis by at least two mechanisms, and that these mechaniams can be modulated by various exogenous agents.
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Dissertation (Ph.D.)--Boston University
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