Sela Shifra, Shurtz-Swirski Revital, Awad Jamal, Shapiro Galina, Nasser Lubna, Shasha Shaul M, Kristal Batya
Eliachar Research Laboratory, Nephrology and Hypertension Unit, Internal Department VI, Western Galilee Hospital, Nahariya, Israel.
Isr Med Assoc J. 2002 Nov;4(11):1015-9.
Cigarette smoking is a well-known risk factor for the development of endothelial dysfunction and the progression of atherosclerosis. Oxidative stress and inflammation have recently been implicated in endothelial dysfunction.
To assess the concomitant contribution of polymorphonuclear leukocytes to systemic oxidative stress and inflammation in cigarette smokers.
The study group comprised 41 chronic cigarette-smoking, otherwise healthy males aged 45.0 +/- 11.5 (range 31-67 years) and 41 male non-smokers aged 42.6 +/- 11.3 (range 31-65) who served as the control group. The potential generation of oxidative stress was assessed by measuring the rate of superoxide release from separated, phorbol 12-myristate 13-acetate-stimulated PMNL and by plasma levels of reduced (GSH) and oxidized (GSSG) glutathione. Inflammation was estimated indirectly by: a) determining the in vitro survival of PMNL, reflecting cell necrosis; b) in vivo peripheral PMNL counts, reflecting cell recruitment; and c) plasma alkaline phosphatase levels, indicating PMNL activation and degranulation.
PMA-stimulated PMNL from cigarette smokers released superoxide at a faster rate than PMNL from the controls. Smokers had decreased plasma GSH and elevated GSSG levels. In vitro incubation of control and smokers' PMNL in sera of smokers caused necrosis, while control sera improved smoker PMNL survival. Smokers' PMNL counts, although in the normal range, were significantly higher than those of controls. Plasma ALP levels in smokers were significantly higher than in controls and correlated positively with superoxide release and PMNL counts.
Our study shows that PMNL in smokers are primed in vivo, contribution concomitantly to systemic oxidative stress and inflammation that predispose smokers to endothelial dysfunction, and explains in part the accelerated atherosclerosis found in smokers.
吸烟是内皮功能障碍发生和动脉粥样硬化进展的一个众所周知的危险因素。氧化应激和炎症最近被认为与内皮功能障碍有关。
评估多形核白细胞对吸烟者全身氧化应激和炎症的协同作用。
研究组包括41名慢性吸烟的健康男性，年龄45.0±11.5岁（范围31 - 67岁），以及41名年龄42.6±11.3岁（范围31 - 65岁）的男性非吸烟者作为对照组。通过测量从分离的、佛波酯12 -肉豆蔻酸酯13 -乙酸酯刺激的中性粒细胞释放超氧化物的速率以及血浆中还原型（GSH）和氧化型（GSSG）谷胱甘肽水平来评估氧化应激的潜在产生。通过以下方式间接评估炎症：a）测定中性粒细胞的体外存活率，反映细胞坏死；b）体内外周中性粒细胞计数，反映细胞募集；c）血浆碱性磷酸酶水平，表明中性粒细胞活化和脱颗粒。
吸烟者经佛波酯刺激的中性粒细胞释放超氧化物的速率比对照组的中性粒细胞快。吸烟者血浆GSH水平降低，GSSG水平升高。在吸烟者血清中对对照组和吸烟者的中性粒细胞进行体外孵育会导致坏死，而对照血清可提高吸烟者中性粒细胞的存活率。吸烟者的中性粒细胞计数虽然在正常范围内，但显著高于对照组。吸烟者的血浆碱性磷酸酶水平显著高于对照组，且与超氧化物释放和中性粒细胞计数呈正相关。
我们的研究表明，吸烟者的中性粒细胞在体内处于预激活状态，对全身氧化应激和炎症有协同作用，使吸烟者易患内皮功能障碍，部分解释了吸烟者中动脉粥样硬化加速的现象。
