Koehne P, Willam C, Strauss E, Schindler R, Eckardt K U, Bührer C
Department of Neonatology, Charité, Campus Virchow-Klinikum, Humboldt University, D-13353 Berlin, Germany.
Am J Physiol Heart Circ Physiol. 2000 Aug;279(2):H817-24. doi: 10.1152/ajpheart.2000.279.2.H817.
Low oxygen (O(2)) is the key stimulus for expression of vascular endothelial growth factor (VEGF) in several adherent cells. Whether hypoxia also directs the release of VEGF protein from neutrophils (polymorphonuclear neutrophils; PMN) and platelets has not been investigated. We therefore compared VEGF release of platelets, PMN, and human vascular smooth muscle cells (HSMC) in response to hypoxia with that to activators of cellular degranulation. In contrast to HSMC, VEGF release from PMN and platelets or VEGF mRNA expression in PMN was not stimulated under hypoxic conditions (1% O(2)). Hypo- or hyperthermia and acidosis, other conditions potentially associated with ischemic and inflammatory tissue injury, also did not stimulate VEGF secretion from PMN. However, stimulation of platelets with thrombin and of PMN with phorbol 12-myristate 13-acetate induced a time-dependent release of VEGF, peaking after 30 and 60 min, respectively. This was blocked by the degranulation inhibitor pentoxifylline but not by the protein-synthesis inhibitor cycloheximide. We conclude that rapid release of VEGF from platelets and PMN may occur independently of oxygenation during inflammation and hemostasis.
低氧（O₂）是几种贴壁细胞中血管内皮生长因子（VEGF）表达的关键刺激因素。低氧是否也能指导中性粒细胞（多形核中性粒细胞；PMN）和血小板释放VEGF蛋白尚未得到研究。因此，我们比较了血小板、PMN和人血管平滑肌细胞（HSMC）在低氧条件下与细胞脱颗粒激活剂刺激下的VEGF释放情况。与HSMC不同，在低氧条件（1% O₂）下，PMN和血小板的VEGF释放或PMN中的VEGF mRNA表达未受到刺激。体温过低或过高以及酸中毒等其他可能与缺血和炎症组织损伤相关的情况，也未刺激PMN分泌VEGF。然而，用凝血酶刺激血小板以及用佛波醇12 - 肉豆蔻酸酯13 - 乙酸酯刺激PMN会诱导VEGF的时间依赖性释放，分别在30分钟和60分钟后达到峰值。这被脱颗粒抑制剂己酮可可碱阻断，但未被蛋白质合成抑制剂放线菌酮阻断。我们得出结论，在炎症和止血过程中，血小板和PMN中VEGF的快速释放可能与氧合无关。
