Table 1.
Chemokines implicated in Chronic Obstructive Pulmonary Disease (COPD).
| Attracting Cells | Expressing Cells | Chemokine | Receptor | Studied Site/Organ | Model | Result | Ref. |
|---|---|---|---|---|---|---|---|
| Neutrophils > monocytes | Macrophages, mast cells | CXCL1 (GROalpha) | CXCR2 > CXCR1 | Sputum | Human | Increased in COPD compared to IP | [55,56] |
| Neutrophils > monocytes | Macrophages, mast cells | CXCL2 (MIP-2, GRObeta) | CXCR2 | BALF | Mouse | Increased in COPD compared to control | [57] |
| Neutrophils > monocytes | Alveolar macrophages, epithelial cells, platelets | CXCL5 (epithelial neutrophil-activating peptide 78) | CXCR2 | Bronchial epithelium | Human | Increased at the mRNA level in severe exacerbatory COPD patients compared to stable COPD patients and controls | [58] |
| Neutrophils > monocytes | Inflammatory cells, fibroblasts, endothelial cells, platelets | CXCL7 (truncation product of CTAP-III) | CXCR2 | Bronchial mucosa | Human | Increased number of CXCL7+ cells/mRNA level in stable severe COPD patients compared to healthy controls | [59] |
| Neutrophils > monocytes | Neutrophils, epithelial cells, macrophages, fibroblasts, airway smooth muscle cells | CXCL8 (IL-8) | CXCR1 CXCR2 CCR2 |
Lung fibroblasts | Human | Increased | [58,60,61,62,63,64,65,66,67] |
| Blood | Increased in COPD compared to asthma | ||||||
| Induced sputum | Increased in COPD patients compared to controls (smokers and nonsmokers) and asthma | ||||||
| Lung | Increased in bronchiolar epithelium at the mRNA level | ||||||
| Th1 lymphocytes, Tc1 lymphocytes, B lymphocytes | Macrophages, dendritic cells, bronchial epithelial cells | CXCL9 (MIG) | CXCR3 | Lung section | Human | CXCL9 expressed in and around lung lymphoid follicles; - CXCR3 expressed in lung lymphoid follicles, correlated with GOLD stage, inversely correlated with FEV1 | [68,69,70] |
| Sputum | Human | Increased in the sputum of patients with COPD when compared with nonsmokers (but not smokers without obstruction) | |||||
| Bone marrow | Guinea pig | Decreased at the mRNA level in the bone marrow of CS-exposed guinea pigs compared to controls | |||||
| Th1 lymphocytes, Tc1 lymphocytes, B lymphocytes | Macrophages, dendritic cells, bronchial epithelial cells | CXCL10 (IP-10) | CXCR3 | Lung section | Human | CXCL10 expressed in and around lung lymphoid follicles; also in bronchiolar epithelium, airway smooth muscle cells | [68,69,71,72,73] |
| Serum | Elevated in COPD patients compared to controls | ||||||
| Sputum | Increased in the sputum of patients with COPD when compared with nonsmokers (but not smokers without obstruction) | ||||||
| Th1 lymphocytes, Tc1 lymphocytes, B lymphocytes | Macrophages, dendritic cells, bronchial epithelial cells | CXCL11 (I-TAC) | CXCR3 | Sputum | Human | Increased in the sputum of patients with COPD when compared with nonsmokers (but not smokers without obstruction) | [68] |
| BM-MSCs, EPCs, HPCs, lymphocytes, fibrocytes | Inflammatory cells, epithelial and endothelial cells, perivascular stromal cells, BM-MSCs, | CXCL12 (SDF-1) | CXCR4, CXCR7 | Bone marrow | Human | Reduced in COPD BM-MSCs compared to control subjects (mRNA level) | [74,75,76] |
| Blood | Mouse | Enhanced chemosensitivity to CXCL12 of fibrocytes from exacerbating COPD level of CXCL12 decreased in CS-exposed murine lungs | |||||
| Naïve B cells | Follicular dendritic cells, B cells | CXCL13 | CXCR5 | Serum | Human | Decreased in the serum of BMS-COPD subjects compared to controls | [77] |
| Leucocytes, mononuclear cells | Endothelial, epithelial, and smooth muscle cells; macrophages, dendritic cells, B and T cells, and platelets (transmembrane chemokine) | CXCL16 | CXCR6 | Blood | Human | Percentage of CXCL16 (and CXCR6) expressing platelets is increased in COPD patients compared to controls | [78] |
| Monocytes > T lymphocytes, fibrocytes | Alveolar macrophages, T cells, endothelial and epithelial cells | CCL2 (MCP-1) | CCR2 | Blood | Human | Increased in COPD with prevalent emphysema compared to control subjects | [56,65,66,79,80] |
| Sputum | Human | Increased in COPD compared to nonsmokers and healthy smokers | |||||
| Lung | Human | Increased in bronchiolar epithelium at the mRNA level | |||||
| BALF and lung homogenate | Mouse | Increased in CSE-treated mice compared to control group | |||||
| Macrophages; Th2 lymphocytes | Macrophages, lymphocytes, fibroblasts, epithelial cells | CCL3 (MIP-1alpha) | CCR1, 4, 5 | Induced sputum | Human | Increased in COPD patients compared to controls | [81] |
| Macrophages, neutrophils and dendritic cells; memory T cells; basophils, eosinophils; fibrocytes | Endothelial cells, smooth muscle cells; T lymphocytes, epithelial cells | CCL5 (RANTES) | CCR1, 3, 5 | Bronchial mucosa | Human | Increased number of CCL5+ cells/mRNA level in stable severe COPD patients compared to healthy controls | [59,68] |
| Sputum | Increased in the sputum of patients with COPD when compared with nonsmokers (but not smokers without obstruction) | ||||||
| Eosinophils; Th2 lymphocytes | Epithelial cells, endothelial cells, T lymphocytes, macrophages, eosinophils | CCL11 (Eotaxin-1) | CCR3 | BALF | Human | Increased in BALF of COPD with a bronchodilator response, and correlated with emphysema | [82,83,84,85] |
| Blood | Increased in COPD (particularly rapidly progressive) compared to control subjects, and associated with decreased FEV1% and FEV1/FVC ratio | ||||||
| Lamina propria | Number of eotaxin+ and CCR3+ cells significantly higher in exacerbated COPD compared to healthy subjects | ||||||
| T cells, monocytes;Eosinophils; endothelial cells | Basophils, lung leucocytes, alveolar macrophages, airway smooth muscle cells | CCL15 | CCR1 > CCR3 | Serum | Human | Decreased in the serum of BMS-COPD subjects compared to controls | [77] |
| TH2 lymphocytes | Dendritic cells, activated Langerhans cells, airway epithelial cells | CCL17 (TARC) | CCR4 | Serum | Human | Decreased in the serum of BMS-COPD subjects compared to controls rs9302690 SNP significantly associated with higher CCL17 levels in COPD patients | [77,82] |
| T lymphocytes, immature dendritic cells | Dendritic cells, monocytes, alveolar macrophages | CCL18 (PARC/MIP-4/AMAC-1/DC-CK1/SCYA-18) | CCR8 | Serum | Human | Increased in COPD compared to non-obstructive smokers and never smokers | [86,87] |
| Naïve T lymphocytes, mature dendritic cells | Fibroblasts | CCL19 | CCR7 | Bone marrow | Human | Reduced in COPD BM-MSCs compared to control subjects (mRNA level) | [75] |
| Dendritic cells; neutrophils, lymphocytes | Airway epithelial cells, macrophages | CCL20 (MIP-3alpha) | CCR6 | Total lung and induced sputum | Human | Increased at the mRNA level in total lung and at the protein level in induced sputum, compared to never smokers and smokers without COPD | [88] |
| T lymphocytes, mature dendritic cells | Lymphatic endothelial cells | CCL21 | CCR7 | Bone marrow | Human | Reduced in COPD BM-MSCs compared to control subjects (mRNA level) | [75] |
| Memory T lymphocytes | Epithelial cells? (highly produced by keratinocytes in the skin) | CCL27 | CCR10 | Serum | Human | Decreased in the serum of BMS-COPD subjects compared to controls | [77] |
| T lymphocytes, monocytes | Mature dendritic cells, endothelial cells | CX3CL1 (Fractalkin) | CX3CR1 | Serum | Human | Associated with emphysema in chinese COPD patients | [89] |
COPD: chronic obstructive pulmonary disease; CS: cigarette smoke; IP: interstitial pneumonia; BM-MSCs: bone marrow mesenchymal stem cells; BALF: broncho-alveolar lavage fluid; BMS: biomass smoke; EPCs: endothelial progenitor cells, HPCs: hematopoietic stem cells, SNP: single nucleotide polymorphism. Expressing cells are from the systemic circulation or lung cells (other organs are not mentioned) and based on human available data. Additional references for chemokines receptors [24] and attracted cells [90].