title: An immune basis for lung parenchymal destruction in chronic obstructive pulmonary disease and emphysema.
abstract: BACKGROUND
  Chronic obstructive pulmonary disease and emphysema are a frequent result of long-term smoking, but the exact mechanisms, specifically which types of cells are associated with the lung destruction, are unclear.
  
  
  RESULTS
  We studied different subsets of lymphocytes taken from portions of human lungs removed surgically to find out which lymphocytes were the most frequent, which cell-surface markers these lymphocytes expressed, and whether the lymphocytes secreted any specific factors that could be associated with disease. We found that loss of lung function in patients with chronic obstructive pulmonary disease and emphysema was associated with a high percentage of CD4+ and CD8+ T lymphocytes that expressed chemokine receptors CCR5 and CXCR3 (both markers of T helper 1 cells), but not CCR3 or CCR4 (markers of T helper 2 cells). Lung lymphocytes in patients with chronic obstructive pulmonary disease and emphysema secrete more interferon gamma--often associated with T helper 1 cells--and interferon-inducible protein 10 and monokine induced by interferon, both of which bind to CXCR3 and are involved in attracting T helper 1 cells. In response to interferon-inducible protein 10 and monokine induced by interferon, but not interferon gamma, lung macrophages secreted macrophage metalloelastase (matrix metalloproteinase-12), a potent elastin-degrading enzyme that causes tissue destruction and which has been linked to emphysema.
  
  
  CONCLUSIONS
  These data suggest that Th1 lymphoctytes in the lungs of people with smoking-related damage drive progression of emphysema through CXCR3 ligands, interferon-inducible protein 10, and monokine induced by interferon.
authors.affiliation: Department of Medicine, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Sandra
authors.initials: S
authors.lastname: Grumelli
authors.forename: David B
authors.initials: DB
authors.lastname: Corry
authors.forename: Li-Zhen
authors.initials: LZ
authors.lastname: Song
authors.forename: Ling
authors.initials: L
authors.lastname: Song
authors.forename: Linda
authors.initials: L
authors.lastname: Green
authors.forename: Joseph
authors.initials: J
authors.lastname: Huh
authors.forename: Joan
authors.initials: J
authors.lastname: Hacken
authors.forename: Rafael
authors.initials: R
authors.lastname: Espada
authors.forename: Remzi
authors.initials: R
authors.lastname: Bag
authors.forename: Dorothy E
authors.initials: DE
authors.lastname: Lewis
authors.forename: Farrah
authors.initials: F
authors.lastname: Kheradmand
mesh_terms: D000368:Aged; D054357:Chemokine CXCL10; D019743:Chemokines, CXC / Q000502:physiology; D016207:Cytokines / Q000502:physiology; D018450:Disease Progression; D005260:Female; D006801:Humans; D016131:Lymphocyte Subsets; D016676:Macrophages, Alveolar / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000276:immunology* / Q000503:physiopathology*; D011656:Pulmonary Emphysema / Q000276:immunology* / Q000503:physiopathology*; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000502:physiology; D012907:Smoking / Q000009:adverse effects; D018417:Th1 Cells / Q000276:immunology*; D014057:Tomography, X-Ray Computed
chemical_list: C515187:CXCR3 protein, human; D054357:Chemokine CXCL10; D019743:Chemokines, CXC; D016207:Cytokines; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine