Cigarette smoking causes sequestration of polymorphonuclear leukocytes released from the bone marrow in lung microvessels

Studies from our laboratory have shown that chronic cigarette smoke exposur e causes a neutrophilia associated with a shortening of the mean transit ti me of polymorphonuclear leukocytes (PMN) though the postmitotic pool of the marrow. The present study was designed to test the hypothesis that PMN new ly released from bone marrow by smoke exposure preferentially sequestered i n pulmonary microvessels. The thymidine analogue 5'-bromo-2'-deoxyuridine ( BrdU) was used to label dividing PMN in the marrow of rabbits; their appear ance in the circulation was measured using immunocytochemistry, and their s equestration in lung tissue was determined using standard morphometric tech niques. Animals exposed to 11 d of cigarette smoke (n = 6) compared with sh am-exposed control animals (n = 4) showed no increase in circulating PMN co unts 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 ( pMN(BrdU)) 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-e xposed animals (51.7 +/- 3.4 X 10(7)/ml tissue) than in those of control an imals (25.1 +/- 1.8 X 10(7)/ml tissue) (P < 0.05) and a higher percentage o f these cells were pMN(BrdU) (smoking, 16.9 +/- 2.3% versus control, 9.6 +/ - 0.4%; P < 0.05). The percentage of pMN(BrdU) in the gravity-independent r egions (11.7 +/- 1.9%) of the lung was higher than gravity-dependent region s (7.8 +/- 1.8%) in the smoke-exposure group (P < 0.05). Transmission elect ron 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 pulmona ry microvessels and speculate that these PMN may contribute to the alveolar wall damage associated with smoke-induced lung emphysema.