Research article

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 Liu^1,2 , Hannah R Bishop³ , Diane E Renaud³ , Richard M Palmer⁴ , Abdel Soussi-Gounni⁵ and David A Scott^3,6

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

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

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

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

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

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

author email corresponding author email

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

Published:	15 April 2008

Abstract

Background

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.

Results

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).

Conclusion

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.