Polymorphonuclear leukocytes (PMN) when activated release products that can potentially injure endothelial cells or alter endothelial function. Exposure of cultured human umbilical vein endothelial cells to cathepsin G and elastase isolated from human PMN at concentrations reached in vivo (100 ng/mL to 10 micrograms/mL) selectively inhibited thrombin-induced prostacyclin production and the thrombin-induced rise in cytosolic free calcium ([Ca++]i) concentration. These proteases also blocked thrombin-induced release of arachidonic acid from prelabeled endothelial cells (EC). In contrast, induction of prostacyclin (PGI2) production by arachidonate, histamine, or the calcium ionophore A23187 was not altered by treatment of EC with these proteases. The effects of the proteases were concentration-dependent, were blocked by serum or serum protease inhibitors, and were reversed when the endothelial cells were further cultured for 24 hours in the absence of the proteases. Elastase, but not cathepsin G, also produced detachment of endothelial cells. Thus, the major leukocyte proteases selectively suppress thrombin-induced prostacyclin production by human vascular endothelial cells and may alter the hemostatic balance at sites of PMN activation.
Rat aortic endothelial cells have been isolated by the explantation technique and grown in culture. They have been identified morphologically using standard staining techniques, biochemically by identification of angiotensin convertase and have been positively stained for Factor VIII-related antigen by immunofluorescence using both anti-human and anti-rat Factor VIII antibodies. The explantation technique is a successful alternative to enzyme digestion which is not applicable to rat aortic endothelial cells because of the nature of their attachment to the subendothelial layer.
I A comparative study of the responses of the gastrointestinal tract of the guinea-pig and of the fruiteating bat Eidolon helvum to transmural nerve stimulation (TNS) was made. 2 The stomach and rectum of the guinea-pig, the bat and the guinea-pig ileum contracted in response to TNS. These contractions were cholinergic in nature because atropine blocked and physostigmine potentiated them. 3 Tetrodotoxin reversibly abolished these contractions suggesting that they were nerve-mediated. 4 The bat isolated ileum usually responded to TNS with mixed motor and inhibitory components. In some cases, there were only motor or inhibitory components. 5 The motor component was abolished by atropine and potentiated by physostigmine. However, the inhibitory component was non-adrenergic and non-cholinergic (NANC). 6 Tetrodotoxin abolished the motor component without influencing the inhibitory component. 7 Periarterial nerve stimulation of the bat ileum produced a relaxation that was blocked by bretylium, propranolol, phentolamine, reserpine and tetrodotoxin. 8 It is concluded that the bat gastrointestinal smooth muscle, like the guinea-pig, has cholinergic excitatory innervation; however, the bat ileum has both a cholinergic excitatory innervation and a nonadrenergic and non-cholinergic inhibitory component.
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