Figures
- Figure 1
Inflammatory and immune cells involved in asthma. Inhaled allergens activate sensitized mast cells by crosslinking surface-bound immunoglobulin (Ig)E molecules to release several bronchoconstrictor mediators, including cysteinyl-leukotrienes (cys-LT) and prostaglandin D2 (PGD2). Epithelial cells release stem-cell factor (SCF), which is important for maintaining mucosal mast cells at the airway surface. Allergens are processed by myeloid dendritic cells, which are conditioned by thymic stromal lymphopoietin (TSLP) secreted by epithelial cells and mast cells to release the chemokines CC- 31 chemokine ligand (CCL)17 and CCL22, which act on CC-chemokine receptor 4 (CCR4) to attract T helper 2 (Th-2) cells. Th-2 cells have a central role in orchestrating the inflammatory response in allergy through the release of interleukin-4 (IL-4) and IL-13 (which stimulate B-cells to synthesise IgE) IL-5 (which is necessary for eosinophilic inflammation) and IL-9 (which stimulates mast-cell proliferation). Epithelial cells release CCL11, which recruits eosinophils via CCR3. Patients with asthma may have a defect in regulatory T-cells (Treg), which may favour further Th2-cell proliferation.
- Figure 2
Inflammatory and immune cells involved in chronic obstructive pulmonary disease (COPD). Inhaled cigarette smoke and other irritants activate epithelial cells and macrophages to release several chemotactic factors that attract inflammatory cells to the lungs, including CC-chemokine ligand 2 (CCL2), which acts on CC-chemokine receptor 2 (CCR2) to attract monocytes, CXC-chemokine ligand 1 (CXCL1) and CXCL8, which act on CCR2 to attract neutrophils and monocytes (which differentiate into macrophages in the lungs) and CXCL9, CXCL10 and CXCL11, which act on CXCR3 to attract T helper 1 (Th1) cells and type 1 cytotoxic T-cells (TC1 cells). These inflammatory cells together with macrophages and epithelial cells release proteases, such as matrix metalloproteinase 9 (MMP9), which cause elastin degradation and emphysema. Neutrophil elastase also causes mucus hypersecretion. Epithelia cells and macrophages also release transforming growth factor (TGF), which stimulates fibroblast proliferation, resulting in fibrosis in the small airways.
- Figure 3
Contrasting histopathology of asthma and chronic obstructive pulmonary disease (COPD). A small airway from a patient who died from asthma and a similar sized airway from a patient with severe COPD are shown. There is an infiltration with inflammatory cells in both diseases. The airway smooth muscle (ASM) layer is thickened in asthma but only to a minimal degree in COPD. The basement membrane (BM) is thickened in asthma due to collagen deposition (subepithelial fibrosis) but not in COPD, whereas in COPD collagen is deposited mainly around the airway (peribronchiolar fibrosis). The alveolar attachments are intact in asthma, but disrupted in COPD as a result of emphysema. Images courtesy of J. Hogg (Vancouver, Canada).
- Figure 4
CD8+ T-cells in chronic obstructive pulmonary disease (COPD). Epithelial cells and macrophages are stimulated by interferon-γ (IFN) to release the chemokines CXC-chemokine ligand 9 (CXCL9), CXCL10 and CXCL11, which together act on CXC-chemokine receptor 3 (CXCR3) expressed on T helper 1 (Th1) cells and type 1 cytotoxic T (Tc1) cells to attract them into the lungs. Tc1 cells, through the release of perforin and granzyme B, induce apoptosis of type 1 pneumocytes, thereby contributing to emphysema. IFN released by Th1 and Tc1 cells then stimulates further release of CXCR3 ligands, resulting in a persistent inflammatory activation.
Tables
- Table 1 Differences in histopathology between asthma and chronic obstructive pulmonary disease (COPD) airways
Asthma COPD Mast cells Increased and activated Normal Dendritic cells Increased Uncertain Eosinophils Increased Normal Neutrophils Normal Increased Lymphocytes Th2 Th1, Tc1 Epithelium Often shed Pseudostratified Goblet cells Increased Increased Airway smooth muscle Increased Minimal increase Airway vessels Increased Not increased Fibrosis Subepithelial Peribronchiolar Th: T-helper; Tc: T-cytotoxic.
- Table 2 Comparison between asthma and chronic obstructive pulmonary disease (COPD) inflammation patterns
Asthma COPD Mild Severe Exacerbation Mild Severe Exacerbation Neutrophils 0 ++ ++++ ++ +++ ++++ Eosinophils + ++ +++ 0 0 + Mast cells ++ +++ +++? 0 0 ? Macrophages + + ? +++ ++++ ++++ T-lymphocytes TH2++, iNKT?? Th1+, Th2+, Tc1+, Tc2, Th17? ? Tc1+ Tc1+++, Th1+++, Th17? ? B-lymphocytes B-ϵ B-ϵ ? + +++ ? Dendritic cells + ? ? +? +? ? Chemokines CCL11 CXCL8+ CXCL8++ CXCL8+, CXCL1+, MCP-1 CXCL8++ CXCL8+++ Cytokines IL-4, IL-5, IL-13 TNF-α ? TNF-α+ TNF-α++ TNF-α+++ Lipid, mediators LTD4++, PGD2+ LTB4++ PGD2+ ? LTB4+ LTB4++ LTB4+++ Oxidative stress 0 ++ +++ ++ +++ ++++ Steroid response ++++ ++ + 0 0 0 0: no response; + to ++++: degree of magnitude; ?: uncertain. Th: T-helper; NKT: natural killer T-cell; CCL: CC-chemokine ligand; IL: interleukin; Tc: T-cytotoxic cell; CXCL: CXC motif ligand; TNF: tumour hecrosis factor; MCP: monocyte chemotactic protein.
