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The influence of nicotine on granulocytic differentiation – Inhibition of the oxidative burst and bacterial killing and increased matrix metalloproteinase-9 release

Minqi Xu1, James E Scott1, Kan-Zhi Liu12, Hannah R Bishop3, Diane E Renaud3, Richard M Palmer4, Abdel Soussi-Gounni5 and David A Scott36*

Author affiliations

1 Department of Oral Biology, University of Manitoba, Winnipeg, Canada

2 Institute for Biodiagnostics, National Research Council, Winnipeg, Canada

3 Oral Health and Systemic Disease Research Group, University of Louisville, Louisville, USA

4 Department of Preventive Dentistry, King's College London, London, UK

5 Department of Immunology, University of Manitoba, Winnipeg, Canada

6 Department of Toxicology and Pharmacology, University of Louisville, Louisville, USA

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Citation and License

BMC Cell Biology 2008, 9:19  doi:10.1186/1471-2121-9-19

Published: 15 April 2008



Neutrophils leave the bone marrow as terminally differentiated cells, yet little is known of the influence of nicotine or other tobacco smoke components on neutrophil differentiation. Therefore, promyelocytic HL-60 cells were differentiated into neutrophils using dimethylsulfoxide in the presence and absence of nicotine (3-(1-methyl-2-pyrrolidinyl) pyridine). Differentiation was evaluated over 5 days by monitoring terminal differentiation markers (CD11b expression and formazan deposition); cell viability, growth phase, kinetics, and apoptosis; assessing cellular morphology and ultrastructure; and conformational changes to major cellular components. Key neutrophil effector functions (oxidative burst, bacterial killing, matrix metalloproteinase release) were also examined.


Nicotine increased the percentage of cells in late differentiation phases (metamyelocytes, banded neutrophils and segmented neutrophils) compared to DMSO alone (p < 0.05), but did not affect any other marker of neutrophil differentiation examined. However, nicotine exposure during differentiation suppressed the oxidative burst in HL-60 cells (p < 0.001); inhibited bacterial killing (p < 0.01); and increased the LPS-induced release of MMP-9, but not MMP-2 (p < 0.05). These phenomena may be α-7-acetylcholine nicotinic receptor-dependent. Furthermore, smokers exhibited an increased MMP-9 burden compared to non-smokers in vivo (p < 0.05).


These findings may partially explain the known increase in susceptibility to bacterial infection and neutrophil-associated destructive inflammatory diseases in individuals chronically exposed to nicotine.