Table 2.
Representative biomarkers of macrophage activation and metabolic dysfunction in chronic lung diseases.
| Disease | Biomarker | Source | Macrophage-derived? | Clinical Relevance |
|---|---|---|---|---|
| Asthma | Arginase-1 | BALF macrophage | Yes (M2 macrophage) | Promotes collagen synthesis, airway fibrosis |
| YKL-40 (CHI3L1) 67 | Serum/BALF | Yes (macrophages, others) | Correlates with asthma severity and airway remodeling | |
| FeNO 160 | Breath | Partially (epithelium via iNOS; modulated by Arg1) | Elevated in allergic (type 2) asthma; indicates airway eosinophilic inflammation; influenced by macrophage arginase activity | |
| LTB4 | Sputum/BALF | Yes (macrophages, neutrophils) | Increased in asthmatic airways; contributes to bronchoconstriction and inflammation | |
| 15-HETE & Lipoxin A4 | BALF | Yes (macrophages) | Reduced in asthma; anti-inflammatory and pro-resolving lipid mediators | |
| CCL17 (TARC) | BALF | Yes | Macrophage-secreted chemokine; eosinophil/T cell recruitment | |
| Periostin | Serum | No | Biomarker of type 2 inflammation | |
| COPD | CXCL8 (IL-8) | Sputum | Yes (macrophages, epithelium) | Markedly elevated in COPD sputum; drives neutrophil recruitment |
| MMP-9, MMP-12 | BALF/Sputum | Yes (macrophages, neutrophils) | Promote elastin degradation and emphysema progression | |
| 3-Nitrotyrosine | Sputum cells | Yes (macrophages) | Reflects peroxynitrite (ONOO-)-mediated oxidative stress | |
| Hemosiderin 161 | BALF macrophages | Yes (indicative) | Indicates iron overload and oxidative injury | |
| SP-A, SP-D 162 | Serum | No | General marker of lung injury and exacerbations | |
| IPF | CCL18/PARC 163, 164 | Serum, BALF | Yes (M2 macrophages) | Reflects profibrotic M2 activation; predicts poor survival and faster disease progression |
| YKL-40 (CHI3L1) | Serum, BALF | Yes (macrophages, others) | Associated with fibrosis and matrix remodeling | |
| MMP-7 165 | Serum | Partially (epithelium, macrophages) | Indicates active epithelial injury and remodeling | |
| KL-6 (MUC1) 164, 166, 167 | Serum | No (alveolar type Ⅱ cells) | Widely used diagnostic and prognostic biomarker for ILDs | |
| SP-D 164, 168 | Serum | No | Reflect epithelial injury and surfactant disturbance | |
| Reduced itaconate (ACOD1 product) 114 | BALF macrophages | Yes | Loss of anti-inflammatory metabolite regulation; linked to persistent activation | |
| CD44 169 | BALF/lung tissue | Partially (macrophages, fibroblasts) | Regulates macrophage-fibroblast crosstalk; associated with fibrosis progression | |
| CX3CL1 (fractalkine) 170 | Serum, BALF | Yes (Endothelium, macrophages) | Potential diagnostic biomarker; correlates with IPF progression | |
| S100A8/A9/A12 (S100 family) 171 | Serum, BALF | Partially (macrophages, neutrophils) | Associated with inflammation, oxidative stress, and fibrogenesis |
Abbreviations: BALF, bronchoalveolar lavage fluid; FeNO, fractional exhaled nitric oxide; LTB4, leukotriene B4; 15-HETE, 15-hydroxyeicosatetraenoic acid; CCL17, chemokine (C-C motif) ligand 17; TARC, thymus and activation-regulated chemokine; MMP, matrix metalloproteinase; SP, surfactant protein; CCL18/PARC, pulmonary and activation-regulated chemokine; KL-6, Krebs von den Lungen-6, a mucin 1 glycoprotein; ILDs, interstitial lung diseases; ACOD1, aconitate decarboxylase 1.