Abstract
The microvascular response to topical application of leukotriene B4(LTB4) in the hamster cheek pouch was investigated using a combined intravital-electron microscopic approach. In an effort to gain insight into the cellular basis of the reported neutrophil-dependent increase in vascular permeability evoked by LTB4, experiments were undertaken to determine the morphological impact of diapedesis on the integrity of the vascular wall. A 3-minute topical application of LTB4 (1.0 μM) to the everted pouch resulted in marked leukocyte adherence to the endothelium of postcapillary and larger venules. Extravasation of fluorescein-labeled albumin in response to LTB4 was diffuse in appearance surrounding these venules or manifested as a subtle increase over background fluorescence. Micrographs from selected venular regions of LTB4-treated pouches revealed neutrophils in all stages of diapedesis. Endothelial cells (ECs) to which neutrophils had adhered displayed a prominent organization of microfilaments, occasional microtubules and numerous plasmalemmal vesicles at the neutrophil-endothelial interface. Serial sections inferred neutrophil emigration through interendothelial junctions. ECs appeared to envelope the trailing ends of diapedesing cells, thereby forming interendothelial bridges which effectively resealed the endothelial barrier. The intimate associations between neutrophils and ECs during diapedesis and the absence of any morphologic barrier defect despite the dramatic exodus of cells from the vasculature in response to LTB4 argued against transendothelial transport of macromolecules in the wake of or carried by emigrating neutrophils. Studies employing fluorescein-labeled horseradish peroxidase (HRP) as an intravascular, fluorescent, electron-dense tracer also failed to reveal diapedesis-associated extravasation after exposure to LTB4. Junctional permeability and vesicular transport were not significantly enhanced. However, LTB4-treated peroxidase-injected hamsters revealed venules characterized by occasional ECs which demonstrated positive plasmalemmal and cytoplasmic reaction product. Interstitial macrophages in these pouches were strongly peroxidase positive, moreso than those from LTB4-treated, saline-injected hamsters...
Lewis, Ruth Ellen (1985). Emigration of polymorphonuclear leukocytes and macromolecular extravasation induced by leukotriene B₄ : a combined intravital-ultrastructural study. Texas A&M University. Texas A&M University. Libraries. Available electronically from
https : / /hdl .handle .net /1969 .1 /DISSERTATIONS -777898.