Effects Of Polymorphonuclear Leukocytes Research Articles

Bovine polymorphonuclear leukocytes increase sensitivity to noradrenaline in isolated mesenteric arteries.

1. The effects of polymorphonuclear leukocytes (PMN) on vascular function to (-)-noradrenaline were examined in vitro. Purified bovine PMN were incubated in siliconized organ baths containing rings of bovine mesenteric arteries, after which a concentration-effect curve in response to (-)-noradrenaline was obtained. 2. PMN-derived products induced a long lasting concentration-dependent contraction of the blood vessels generating 24.4 +/- 6.8% of the maximal tension to (-)-noradrenaline at a cell concentration of 2.5 x 10(6) ml-1. The contractile response was also found in endothelium-denuded vascular rings. 3. PMN present in the organ bath caused an increase in the sensitivity of vascular rings to (-)-noradrenaline. At a cell number of 2.5 x 10(6) PMN ml-1 the pD2-value for (-)-noradrenaline was augmented 0.40 +/- 0.05 (P less than 0.001), while total contraction at the highest concentration (-)-noradrenaline was not affected. This increase in sensitivity was dependent on an intact endothelium. 4. The increase in sensitivity to (-)-noradrenaline by PMN was inhibited by superoxide dismutase, but not by catalase, dimethylthiourea, indomethacin or nordihydroguaiaretic acid. The non-stimulated bovine PMN produced oxygen radicals as measured by chemiluminescence. 5. Simultaneous incubation of PMN and (-)-noradrenaline with arterial rings induced an increase in the release of prostacyclin, measured by an elevated concentration of 6-keto-prostaglandin F1 alpha in the supernatant. 6. It is concluded that PMN can increase vascular tone directly or indirectly probably via the interaction of PMN-derived superoxide anions with endothelium-derived relaxing factor.

Modulation of vascular tone by neutrophils: dependence on endothelial integrity

To determine the influence of polymorphonuclear leukocytes (PMNLs) on vascular smooth muscle tone, isolated human PMNLs (10(4)-10(7) cells/ml) were suspended in a tissue bath with precontracted rat aortic rings with or without endothelium. PMNLs in low concentrations (10(4) and 10(5) cells/ml) caused a mild contraction, and in higher concentrations (10(6) and 10(7) cells/ml) caused a modest relaxation of aortic rings with intact endothelium. In contrast, PMNLs caused a potent concentration-dependent relaxation of deendothelialized rings (P less than 0.01 compared with rings with intact endothelium). The PMNL-induced vascular smooth muscle relaxation was abolished by both hemoglobin and methylene blue and potentiated by both superoxide dismutase and captopril. Although suspension of PMNLs caused release of eicosanoids, thromboxane A2 and prostacyclin, from rings with intact endothelium, neither indomethacin nor the TxA2-endoperoxide receptor antagonist SQ 29548 modified the effects of PMNLs on vascular smooth muscle tone. These observations suggest that unstimulated PMNLs generate a smooth muscle relaxant, which has biological characteristics similar to the endothelium-derived relaxing factor. Since the activity of this PMNL-derived smooth muscle relaxant is more pronounced in deendothelialized vascular segments, it appears that endothelium provides a barrier against vasorelaxation by high concentrations of PMNLs.

Effects of polymorphonuclear leukocytes on endothelial cell growth.

<h2>Abstract</h2> Polymorphonuclear leukocytes and their lysosomal constituents from rabbit and human sources were examined for their influence upon the growth of endothelial cells obtained from human umbilical cords. The endothelial cells were cultured in the presence of freeze thawed extracts of whole PMN-leukocytes, freeze thawed and acid extracts of PMN-leukocyte lysosomes and lysosomal cationic proteins (LCP). Growth stimulatory as well as growth inhibitory activities were found in the lysosomal constituents of PMN-leukocytes.