Inflammatory Mediators - Chronic Obstructive Pulmonary Disease - page 262

Figure 6 Chemotaxis of cytotoxic (CD8 þ ) T-lymphocytes via activation of CXCR3
by the CXC chemokines INF- g inducible protein of 10 kDa (IP-10), monokine
induced by INF- g (Mig) and interferon-inducible I-TAC. The CD8 þ cells may
release performs and granzyme B which may induce apoptosis in alveolar cells and
release IFN- g which in turn activates the release of these chemokines.
(95-97). It is of interest that INF- g stimulates dendritic cells to produce IP-
10 and Mig which then enhances their ability to attract CD8 þ cells (98).
Alveolar macrophages also have the capacity to produce IP-10 and Mig
and result in attraction of CD8 þ T cells (99). Since CD8 þ T cells produce
INF- g , this provides a potential feed-forward amplification loop. The role
of CD8 þ T cells in COPD is not yet certain, but as they have the capacity
to produce performs and granzyme B they might induce apoptosis in alveo-
lar epithelial and endothelial cells, thereby contributing to emphysema
(100,101) (Fig. 6).
C. CC Chemokines
Monocyte chemotactic protein-1 (MCP-1, CCL2) is a CC-chemokine that
activates CCR2 on monocytes and T lymphocytes. The CCR2 may play a
role in COPD, as MCP-1 levels are increased in sputum, bronchoalveolar
lavage, and lungs of patients with COPD (Fig. 5) and MCP-1 is expressed
in alveolar macrophages and epithelial cells (81,90,102). The MCP-1 is a
potent chemoattractant of monocytes and may therefore be involved in
the recruitment of macrophages in COPD. Indeed the chemoattractant
effect of induced sputum from patients with COPD is abrogated by an anti-
body to CCR2. Since macrophages appear to play a critical role in COPD as
a source of elastases and neutrophil chemoattractants, blocking CCR2 may