Am. J. Respir. Crit. Care Med., Vol 154, No. 5, Nov 1996, 1520-1524.
Nicotine enhances expression of the neutrophil elastase gene and protein in a human myeloblast/promyelocyte cell line
LW Armstrong, WN Rom, FT Martiniuk, D Hart, J Jagirdar and M Galdston
Department of Medicine, New York University Medical Center, New York, New York, USA.
The pathogenesis of emphysema is considered to be an imbalance of protease
and antiprotease activity in the lower respiratory tract leading to
uninhibited degradation of lung interstitium by elastolytic enzymes. An
increased amount of the serine protease neutrophil elastase (NE) is though
to play a major role in this degradation. Because the expression of NE is
limited to neutrophil precursors in the bone marrow, we hypothesized that
nicotine, which is readily absorbed from lung and distributed to tissue,
including bone marrow, would increase expression of the NE gene and
protein. HL-60 cells, a myeloblast/promyelocyte cell line, were cultured in
the presence or absence of 0.06 and 0.8 microM nicotine for 5 d. Both
concentrations of nicotine caused a 2.4- to 3.3-fold increase,
respectively, in NE gene expression over unstimulated cells, and NE protein
increased 4.8- to 3.4-fold over unstimulated cells, respectively, similar
to our positive control DMSO. Nicotine did not induce upregulation of the
NE gene by initiating cell differentiation. Both low and high nicotine
concentrations upregulate the NE gene in HL-60 cells leading to increased
NE protein concentration per cell suggesting a pathophysiologic mechanism
for emphysema.
