Leukocyte diapedesis and plasma extravasation after leukotriene B4: lack of structural injury to the endothelium.
Leukotriene B4 (LTB4) is a derivative of arachidonic acid which causes neutrophil diapedesis, endothelial swelling and increased permeability of post-capillary venules. To detect whether these effects are accompanied by degranulation of leukocytes and visible injury to the microvessels, the vasculature of rabbit skeletal muscle (tenuissimus) was exposed to LTB4 (10-20 nM). Some preparations were pre-treated with prostaglandin E1, (PGE1). When leukocytes started to adhere markers of plasma leakage were infused. Ultrastructural examination of leakage areas revealed that neutrophils and eosinophils appeared structurally intact, but many basophils and mast cells had been partially degranulated which indicated that vasoactive substances may have been liberated. However, endothelial gaps, such as may form in response to histamine released during degranulation, were not observed and there was no obvious injury to the endothelial cells. The apparent swelling observed by light microscopy was due to pseudopods of migrating leukocytes. Electron dense markers occurred in some endothelial vesicles and in the vicinity of neutrophils which had reached the abluminal side. These particles are interpreted to have escaped concurrent with leukocyte migration. After treatment with both PGE1 and LTB4 a few post-capillary venules showed endothelial gaps. However, leakage of markers was insignificant where the basement membrane persisted. It is concluded that exposure to LTB4 per se and the resulting leukocyte diapedesis are not structurally damaging to the vasculature.
A
A
Thureson-Klein
P
P
Hedqvist
L
L
Lindbom
D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects*; D002610:Cheek; D006224:Cricetinae; D003594:Cytoplasmic Granules / Q000378:metabolism; D003911:Dextrans / Q000378:metabolism; D004727:Endothelium / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D005293:Ferritins / Q000378:metabolism; D007962:Leukocytes / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D007975:Leukotriene B4 / Q000494:pharmacology*; D046911:Macromolecular Substances; D008854:Microscopy, Electron; D009132:Muscles; D011817:Rabbits; D014699:Venules / Q000473:pathology
D003911:Dextrans; D046911:Macromolecular Substances; D007975:Leukotriene B4; D005293:Ferritins