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Cigarette smoking causes sequestration of polymorphonuclear leukocytes released from the bone marrow in lung
T Terashima1, M E Klut, D English
1University of British Columbia Pulmonary Research Laboratory, St. Paul's Hospital, Vancouver, British Columbia, Canada.
Abstract:
Studies from our laboratory have shown that chronic cigarette smoke exposure causes a neutrophilia associated with a shortening of the mean transit time of polymorphonuclear leukocytes (PMN) though the postmitotic pool of the marrow. The present study was designed to test the hypothesis that PMN newly released from bone marrow by smoke exposure preferentially sequestered in pulmonary microvessels. The thymidine analogue 5'-bromo-2'-deoxyuridine (BrdU) was used to label dividing PMN in the marrow of rabbits; their appearance in the circulation was measured using immunocytochemistry, and their sequestration in lung tissue was determined using standard morphometric techniques. Animals exposed to 11 d of cigarette smoke (n = 6) compared with sham-exposed control animals (n = 4) showed no increase in circulating PMN counts but showed an increase in both the percentage of band cells (smoking, 9.8 +/- 1.1% versus control, 5.5 +/- 0.9%; P < 0.05) and BrdU-labeled PMN (PMNBrdU) in the circulation (smoking, 10.8 +/- 0.6% versus control, 7.5 +/- 0.3%; P < 0.05). There were more PMN sequestered in the lungs of smoke-exposed animals (51.7 +/- 3.4 x 10(7)/ml tissue) than in those of control animals (25.1 +/- 1.8 x 10(7)/ ml tissue) (P < 0.05) and a higher percentage of these cells were PMNBrdU (smoking, 16.9 +/- 2. 3% versus control, 9.6 +/- 0.4%; P < 0.05). The percentage of PMNBrdU in the gravity-independent regions (11.7 +/- 1.9%) of the lung was higher than gravity-dependent regions (7.8 +/- 1.8%) in the smoke-exposure group (P < 0.05). Transmission electron microscopy showed pulmonary capillary endothelial damage with adherent PMN in the smoke-exposure group. We conclude that younger PMN released from the bone marrow by cigarette smoking preferentially sequestered in pulmonary microvessels and speculate that these PMN may contribute to the alveolar wall damage associated with smoke-induced lung emphysema.
Insights
Chronic cigarette smoke exposure causes younger polymorphonuclear leukocytes (PMN) to sequester in lung microvessels. These PMN may contribute to smoke-induced lung damage and emphysema.
Area of Science:
- Pulmonary Medicine
- Cell Biology
- Toxicology
Background:
- Chronic cigarette smoke exposure is linked to neutrophilia and altered polymorphonuclear leukocyte (PMN) kinetics.
- Previous studies suggest smoke exposure affects PMN transit time in bone marrow.
Purpose of the Study:
- To test the hypothesis that PMN newly released from bone marrow by smoke exposure preferentially sequester in pulmonary microvessels.
- To investigate the role of these sequestered PMN in smoke-induced lung injury.
Main Methods:
- Rabbits were exposed to cigarette smoke for 11 days.
- Dividing PMN in bone marrow were labeled with 5'-bromo-2'-deoxyuridine (BrdU).
- Circulating and lung-sequestered PMN, including BrdU-labeled PMN (PMNBrdU), were quantified using immunocytochemistry and morphometric techniques.
Main Results:
- Smoke-exposed animals showed increased band cells and PMNBrdU in circulation.
- Significantly more PMN, particularly PMNBrdU, were sequestered in the lungs of smoke-exposed animals compared to controls.
- Pulmonary capillary endothelial damage and adherent PMN were observed in smoke-exposed animals.
Conclusions:
- Newly released, younger PMN from bone marrow preferentially sequester in pulmonary microvessels following cigarette smoke exposure.
- These sequestered PMN may play a role in the pathogenesis of alveolar wall damage and emphysema associated with smoking.