Central role of alveolar macrophages in COPD. Alveolar macrophages are derived from circulating monocytes
that differentiate within the lung. They secrete many inflammatory proteins that may orchestrate the
inflammatory process in COPD. Neutrophils may be attracted by CXCL8, CXCL1, and leukotriene B4 (LTB4); monocytes
by CCL2, and Tc1; and Th1 lymphocytes by CXCL10, CXC11, and CXCL12. Release of elastolytic enzymes
including matrix metalloproteinases (MMP) and cathepsins causes elastolysis, which contributes to emphysema
together with cytotoxic T cells. Release of TGF-b1 may induce fibrosis of small airways. Macrophages generate
reactive oxygen species (ROS) and nitric oxide (NO), which together form peroxynitrite (ONOO-) and may
contribute to corticosteroid resistance. Defective bacterial phagocytosis may lead to bacterial colonization