The Effect of Cigarette Smoking on Neutrophil Kinetics in Human Lungs

Abstract

Neutrophils may play a part in the pathogenesis of the centrilobular emphysema associated with cigarette smoking. The capillary bed of the lungs concentrates neutrophils approximately 100-fold with respect to erythrocytes, producing a large pool of marginated cells. We examined the effect of cigarette smoking on the kinetics of this pool of cells, using 99mTc-labeled erythrocytes to measure regional blood velocity and 111In-labeled neutrophils to measure the removal of neutrophils during the first passage through the pulmonary circulation, their subsequent washout from the lungs, and the effect of local blood velocity on the number of neutrophils retained in each lung region. We observed no difference in these measurements between subjects who had never smoked (n = 6) and smokers who did not smoke during the study (n = 12). However, subjects who did smoke during the study (n = 12) had a significantly slower rate of washout of radiolabeled neutrophils from the lung (0.08 +/- 0.04 of the total per minute, as compared with 0.13 +/- 0.06 in smokers who did not smoke during the experiment and 0.14 +/- 0.08 in non-smokers) (P = 0.02). We also observed an increase in the regional retention of labeled neutrophils with respect to blood velocity in 5 of the 12 subjects who smoked during the study, but in none of the other subjects. We conclude that the presence of cigarette smoke in the lungs of some subjects increases the local concentration of neutrophils, and suggest that the lesions that characterize emphysema may be a result of the destruction of lung tissue by neutrophils that remain within pulmonary microvessels.

Vitamin C prevents cigarette smoke-induced leukocyte aggregation and adhesion to endothelium in vivo.

“…Long-lived ROS are either generated by phagocytic cells that accumulate in the pulmonary microcirculation in response to CS exposure (10,31) or originate from CS per se (12,13). CS gives rise to a wide array of ROS including superoxide and hydrogen peroxide, derived either from components of cigarette tar (i.e., the quinone/hydroquinone/ semiquinone system) or from the gas-phase, entertaining a steady state in which ROS are continuously formed and destroyed (12,13).…”

The response of human bone marrow to chronic cigarette smoking

“…PMNLs in the marrow are larger and less deformable than those in peripheral blood [41], and when prematurely released are predisposed to sequestration in lung capillaries [20,28]. MACNEE et al [44] have shown that PMNLs are retained in the human lung by cigarette smoking, and recent studies by TERASHIMA et al [24] have shown that immature PMNLs are preferentially sequestered in lung microvessels. Assuming a cardiac output of 5 L .…”

Vitamin C blocks inflammatory platelet-activating factor mimetics created by cigarette smoking.

“…Although the mechanisms by which cigarette smoke contributes to cardiovascular disease are not entirely understood, it has been demonstrated that cigarette smoke and its extracts induce diverse inflammatory events whose cumulative effects could contribute to cigarette smoke-related pathology. For example, cigarette smoke elicits the recruitment and adhesion of circulating leukocytes to the vessel wall (1)(2)(3), the initial step in inflammation (4, 5), emphysema (6), and atherosclerosis (7). Recruitment of leukocytes not only into the pulmonary microcirculation (6,8,9), but also into peripheral vascular beds such as the aorta and striated muscle (1,2), suggests that cigarette smoke elicits the formation of circulating inflammatory mediators.…”

“…For example, cigarette smoke elicits the recruitment and adhesion of circulating leukocytes to the vessel wall (1)(2)(3), the initial step in inflammation (4, 5), emphysema (6), and atherosclerosis (7). Recruitment of leukocytes not only into the pulmonary microcirculation (6,8,9), but also into peripheral vascular beds such as the aorta and striated muscle (1,2), suggests that cigarette smoke elicits the formation of circulating inflammatory mediators. Indeed, monocytes isolated just after smoking are in an activated state (10) and plasma isolated just after smoking activates platelets isolated from nonsmokers (11).…”

“…Cigarette smoke introduces a high burden of radicals into the organism (17, 18) and also stimulates the generation of further radicals and reactive oxygen species from activated leukocytes, many of which are chemotactically attracted and sequestered in the lungs (6,9,13). The increased burden of reactive species in the plasma of smokers results in the consumption of the antioxidant vitamin C (19-21), and subsequently the accumulation of various lipid oxidation products in their bloodstream (22)(23)(24).…”