title: Cigarette smoking causes sequestration of polymorphonuclear leukocytes released from the bone marrow in lung microvessels.
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.
authors.affiliation: University of British Columbia Pulmonary Research Laboratory, St. Paul's Hospital, Vancouver, British Columbia, Canada.
authors.forename: T
authors.initials: T
authors.lastname: Terashima
authors.forename: M E
authors.initials: ME
authors.lastname: Klut
authors.forename: D
authors.initials: D
authors.lastname: English
authors.forename: J
authors.initials: J
authors.lastname: Hards
authors.forename: J C
authors.initials: JC
authors.lastname: Hogg
authors.forename: S F
authors.initials: SF
authors.lastname: van Eeden
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells; D001973:Bromodeoxyuridine; D002196:Capillaries / Q000166:cytology; D002455:Cell Division; D004730:Endothelium, Vascular / Q000166:cytology; D005260:Female; D007150:Immunohistochemistry; D007958:Leukocyte Count; D008168:Lung / Q000098:blood supply*; D008833:Microcirculation / Q000166:cytology*; D008854:Microscopy, Electron; D009504:Neutrophils / Q000502:physiology*; D011650:Pulmonary Alveoli / Q000166:cytology; D011817:Rabbits; D012907:Smoking / Q000009:adverse effects*
chemical_list: D001973:Bromodeoxyuridine