High ICAM-1 gene expression in pulmonary fibroblasts of COPD patients: a reflection of an enhanced immunological function.
Chronic obstructive pulmonary disease (COPD) is characterised by destruction of extracellular matrix (ECM) in parenchymal areas, whereas the bronchial walls can show fibrosis. In addition, an extensive inflammatory process is observed. CD8+ T-cells, located throughout the lung, and epithelial cells in centrally located airways, produce cytokines involved in the inflammatory process. These cytokines may influence the present fibroblasts, the key effectors in the defective ECM repair and maintenance in COPD. The current authors explored the effects of the cytokine microenvironment on cell-cell interaction gene expression in pulmonary fibroblasts of controls (n = 6), and Global Initiative for Chronic Obstructive Lung Disease stage II (n = 7) and stage IV (n = 7) COPD patients. The current authors simulated the in vivo microenvironment using supernatants of CD3/CD28 stimulated CD8+ T-cells isolated from peripheral blood of COPD patients, supernatant of a bronchial-epithelial cell line, or a combination of both. The present data show that fibroblasts of chronic obstructive pulmonary disease patients display an altered response to the cytokine microenvironment, depending on both the disease stage and the central or peripheral location in the lung. Especially adhesion-related genes are upregulated in fibroblasts of chronic obstructive pulmonary disease patients, which can indicate a more pronounced role of fibroblasts in the inflammatory process in chronic obstructive pulmonary disease, possibly resulting in reduced function as effectors of extracellular matrix repair.
Zandvoort
A
A
University Medical Center Groningen, Dept of Pathology and Laboratory Medicine, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
van der Geld
Y M
YM
Jonker
M R
MR
Noordhoek
J A
JA
Vos
J T W M
JT
Wesseling
J
J
Kauffman
H F
HF
Timens
W
W
Postma
D S
DS
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D007107:Immune System; D007249:Inflammation; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis*; D008168:Lung / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism*
D018076:DNA, Complementary; D018799:Intercellular Adhesion Molecule-1