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

Overview

MeSH

  • Computer Systems
  • Gene Expression Profiling
  • Genetic Variation
  • Humans
  • Microarray Analysis
  • Phenotype
  • Phylogeny
  • Pulmonary Disease, Chronic Obstructive
  • Reverse Transcriptase Polymerase Chain Reaction

MeSH Major

  • Macrophages, Alveolar
  • Smoking

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, approximately 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.

publication date

  • April 2006

has subject area

  • Computer Systems
  • Gene Expression Profiling
  • Genetic Variation
  • Humans
  • Macrophages, Alveolar
  • Microarray Analysis
  • Phenotype
  • Phylogeny
  • Pulmonary Disease, Chronic Obstructive
  • Reverse Transcriptase Polymerase Chain Reaction
  • Smoking

Research

keywords

  • Comparative Study
  • Journal Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1007/s00109-005-0008-2

PubMed ID

  • 16520944

Additional Document Info

start page

  • 318

end page

  • 328

volume

  • 84

number

  • 4