Biomedical Engineering Reference
In-Depth Information
Figure 5
Elevated concentrations of growth-related oncogene(GRO)-
a
and MCP-1
in induced sputum of patients with COPD. (From Ref. 90.)
to increased turnover of CXCR2 on monocytes of COPD patients (91). It is
possible that the increased chemotactic response of monocytes to GRO-
a
is
one of the mechanisms leading to increased numbers of alveolar macro-
phages in the lungs of patients with COPD (92) (Fig. 3) and could be one
of the molecular mechanisms of susceptibility to cigarette smoking.
Epithelial cell-derived neutrophil-activating peptide-78 (ENA-78,
CXCL5) is derived predominantly from epithelial cells and also activates
CXCR2 (93), although monocytes do not appear to show an increased che-
motactic response to this chemokine as they do to GRO-
a
(91). The ENA-78
is increased in BAL fluid of COPD patients compared to normal subjects,
but there is no difference between patients with emphysema and normal
smokers (77). A marked increase in expression of ENA-78 has been reported
in epithelial cells during exacerbations of COPD (88).
The mechanisms by which CD8
þ
, and to a lesser extend CD4
þ
cells
accumulate in the airways and lungs of patients with COPD is not yet
understood. However, homing of T cells to the lung must depend upon some
initial activation then adhesion and selective chemotaxis. T cells in periph-
eral airways of COPD patients show increased expression of CXCR3, a
receptor activated by interferon-
g
inducible protein of 10 kDa (IP-10,
CXCL10), monokine induced by interferon-
g
(INF-
g
) (Mig, CXCL9) and
interferon-inducible T cell-
a
chemoattractant (I-TAC, CXCL11). All three
chemokines activate CXCR3, although I-TAC has the highest affinity
(94). The CXCR3 is expressed on T-lymphocytes, particularly of the
CD8
þ
subtype. There is increased expression of IP-10 by bronchiolar epithe-
lial cells and airway smooth muscle cells and this could therefore contribute
to the accumulation of CD8
þ
cells, which preferentially express CXCR3
