Rosengren S, Arfors K E
Pharmacia Experimental Medicine, La Jolla, California 92037.
Am J Physiol. 1990 Oct;259(4 Pt 2):H1288-94. doi: 10.1152/ajpheart.1990.259.4.H1288.
Application of leukotriene B4 (LTB4) to hamster cheek pouches induces neutrophil-dependent vascular leakage of macromolecules as well as leukocyte intravascular adherence and emigration. The effect of inhibitors of neutrophil elastase on these reactions was studied with intravital microscopy. Anesthetized hamsters were pretreated with the elastase inhibitors L 658,758, Eglin C, or dextran sulfate, and LTB4 (10 nM) was superfused over the cheek pouches. Neither Eglin C nor L 658,758 had any effect on the resulting vascular leakage of a macromolecular marker; in contrast, dextran sulfate suppressed this leakage by 85%. None of the compounds affected LTB4-induced leukocyte adherence or neutrophil diapedesis. The inhibitors were able to inhibit both hamster and human neutrophil elastase as estimated in crude neutrophil extracts. These results suggest that neutrophils extravasate and generate vascular leakage without the use of their elastase activity. The inhibitory effect of dextran sulfate on macromolecular leakage may be due to interaction with cationic proteins released from the neutrophils.
将白三烯B4（LTB4）应用于仓鼠颊囊可诱导中性粒细胞依赖性的大分子血管渗漏以及白细胞的血管内黏附和移出。采用活体显微镜研究了中性粒细胞弹性蛋白酶抑制剂对这些反应的影响。对麻醉的仓鼠预先给予弹性蛋白酶抑制剂L 658,758、埃格林C或硫酸葡聚糖，然后将LTB4（10 nM）灌注到颊囊上。埃格林C和L 658,758对由此产生的大分子标记物的血管渗漏均无任何影响；相反，硫酸葡聚糖可将这种渗漏抑制85%。这些化合物均不影响LTB4诱导的白细胞黏附或中性粒细胞渗出。在粗制中性粒细胞提取物中评估发现，这些抑制剂能够抑制仓鼠和人中性粒细胞弹性蛋白酶。这些结果表明，中性粒细胞渗出并产生血管渗漏，而未利用其弹性蛋白酶活性。硫酸葡聚糖对大分子渗漏的抑制作用可能是由于其与从中性粒细胞释放的阳离子蛋白相互作用所致。
