F. Syed et al., CCR7(EBI1) receptor down-regulation in asthma: differential gene expression in human CD4(+) T lymphocytes, QJM-MON J A, 92(8), 1999, pp. 463-471
Citations number
42
Categorie Soggetti
General & Internal Medicine","Medical Research General Topics
Journal title
QJM-MONTHLY JOURNAL OF THE ASSOCIATION OF PHYSICIANS
Asthma is an inflammatory disorder, and the CD4(+) T lymphocyte plays a key
role in mediating the inflammatory response. We used a high-density grid,
hybridization-based, differential gene expression technology to analyse mol
ecular mechanisms underlying in vivo CD4(+) T-cell activation in both stero
id-resistant asthma (SRA) and steroid-sensitive asthma (SSA). Hybridization
of radioactively-labelled first-strand cDNAs prepared from different biolo
gical samples, to identical high-density gridded arrays of PCR amplicons de
rived from cDNA clone inserts immobilized on nylon membranes, was compared
by phosphorimaging. Hybridization data were captured and processed using im
age analysis software that can identify the location and signal intensity o
f each hybridized cDNA. This produces a hierarchy of signals of differing i
ntensities between the two grids, representing differential gene expression
in the two different RNA samples. CCR7 (EBI1), a lymphocyte-specific G-pro
tein-coupled receptor, was down-regulated in the CD4(+) T cells of SRA and
SSA non-atopic, compared to non-asthmatic nonatopic individuals. This obser
vation is intriguing given that CCR7 and its ligand EBI1-Ligand Chemokine (
ELC), may play a role in the migration and homing of normal lymphocytes. Al
so, TNFR2 is up-regulated in both SSA non-atopic and SRA atopic as compared
to non-asthmatic controls. LAMR1 is down-regulated in CD4(+) T cells of SR
A compared to non-asthmatic individuals, irrespective of their atopic statu
s. These could be general phenomena resulting from cytokine release.