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Journal of Molecular Medicine

, Volume 84, Issue 4, pp 318–328 | Cite as

Gene expression profiling of human alveolar macrophages of phenotypically normal smokers and nonsmokers reveals a previously unrecognized subset of genes modulated by cigarette smoking

  • Adriana Heguy
  • Timothy P. O’Connor
  • Karsta Luettich
  • Stefan Worgall
  • Adam Cieciuch
  • Ben-Gary Harvey
  • Neil R. Hackett
  • Ronald G. Crystal
Original Article

Abstract

Cigarette smoking is the leading cause of the respiratory diseases collectively known as chronic obstructive pulmonary disease (COPD). While the pathogenesis of COPD is complex, there is abundant evidence that alveolar macrophages (AM) play an important role. Based on the concept that COPD is a slow-progressing disorder likely involving multiple mediators released by AM activated by cigarette smoke, the present study focuses on the identification of previously unrecognized genes that may be linked to early events in the molecular pathogenesis of COPD, as opposed to factors associated with the presence of disease. To accomplish this, microarray analysis using Affymetrix microarrays was used to carry out an unbiased survey of the differences in gene expression profiles in the AM of phenotypically normal, ∼20 pack-year smokers compared to healthy nonsmokers. Although smoking did not alter the global gene expression pattern of AM, 75 genes were modulated by smoking, with 40 genes up-regulated and 35 down-regulated in the AM of smokers compared to nonsmokers. Most of these genes belong to the functional categories of immune/inflammatory response, cell adhesion and extracellular matrix, proteolysis and antiproteolysis, lysosomal function, antioxidant-related function, signal transduction, and regulation of transcription. Of these 75 genes, 69 have not been previously recognized to be up- or down-regulated in AM in association with smoking or COPD, including genes coding for proteins belonging to all of the above categories, and others belonging to various functional categories or of unknown function. These observations suggest that gene expression responses of AM associated with the stress of cigarette smoking are more complex than previously thought, and offer a variety of new insights into the complex pathogenesis of smoking-induced lung diseases.

Keywords

Chronic obstructive pulmonary disease Molecular pathogenesis Immune response and inflammation 

Notes

Acknowledgements

We thank N Mohamed for help in preparing this manuscript. These studies were supported, in part, by R01 HL074326-01; M01RR00047; and the Will Rogers Memorial Fund.

Supplementary material

109_2005_8_MOESM1_ESM.pdf (50 kb)
Supplemental Table 1 (PDF 51 kb)
109_2005_8_MOESM2_ESM.pdf (375 kb)
Supplemental Fig. 1 (PDF 245 kb)
109_2005_8_MOESM3_ESM.pdf (310 kb)
Supplemental Fig. 2 (PDF 245 kb)

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Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Adriana Heguy
    • 1
  • Timothy P. O’Connor
    • 1
  • Karsta Luettich
    • 1
  • Stefan Worgall
    • 1
    • 2
  • Adam Cieciuch
    • 4
  • Ben-Gary Harvey
    • 3
  • Neil R. Hackett
    • 4
  • Ronald G. Crystal
    • 1
    • 3
    • 4
  1. 1.Department of Genetic MedicineWeill Medical College of Cornell UniversityNew YorkUSA
  2. 2.Department of PediatricsWeill Medical College of Cornell UniversityNew YorkUSA
  3. 3.Division of Pulmonary and Critical Care MedicineWeill Medical College of Cornell UniversityNew YorkUSA
  4. 4.Belfer Gene Therapy Core FacilityWeill Medical College of Cornell UniversityNew YorkUSA

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