Table 1.
Preformed and Newly Synthesized Mediators Released by Human Lung Mast Cells.
| Mediator | Properties | References |
|---|---|---|
| Preformed | ||
| Histamine | Preformed in cytoplasmic granules of human mast cells (≅3 pg/cell) and basophils (≅1 pg/cell). | [64,65] |
| β-tryptase | A tetrameric serine protease, abundant in secretory granules of human mast cells. Tryptase+ mast cells are increased in asthmatics bronchial tissue, and their numbers correlate with airway hyperresponsiveness. Tryptase concentrations in bronchoalveolar lavage (BAL) fluid correlates with asthma severity. |
[89,90,91,92] |
| Chymase | A chymotrypsin-like serine protease stored in human mast cell secretory granules causes matrix destruction and inflammation. | [93,94] |
| Cathepsin G | A serine protease that controls the functional state of immune cells. | [93] |
| Carboxypeptidase A3 | It cleaves several proteins. | [95] |
| Granzyme B | A protease involved in the induction of target cell death. | [96] |
| Matrix metalloproteinases (MMPs) | A family of extracellular proteinases. | [97] |
| Lipid Mediators | ||
| Cysteinyl leukotriene C4 (LTC4) | Human lung mast cells (HLMCs) synthesize LTC4, a potent bronchoconstrictor acting through the activation of cysteinyl leukotriene receptor 1 (CysLTR1) and CysLTR2. | [98,99] |
| Prostaglandin D2 (PGD2) | It activates the CRTh2 receptor on several immune cells. | [100,101] |
| Platelet-activating factor (PAF) | A phospholipid with proinflammatory and vasoactive effects. | [102] |
| Cytokines | ||
| Stem cell factor (SCF) | They exert several proinflammatory and immunomodulatory effects. | [37] |
| TNF-α | [103] | |
| IL-1β | [104] | |
| IL-3 | [105,106] | |
| IL-5 | [107] | |
| IL-6 | [108] | |
| IL-9 | [109] | |
| IL-10 | [57] | |
| IL-11 | [108] | |
| IL-13 | [109,110] | |
| IL-16 | [111] | |
| IL-22 | [112] | |
| Thymic stromal lymphopoietin (TSLP) | [113,114,115] | |
| IL-25/IL-17E | [116] | |
| Granulocyte-macrophage colony-stimulating factor (GM-CSF) | [107] | |
| Vascular endothelial growth factor (VEGF) | [117] | |
| Fibroblast growth factor 2 (FGF-2) | [118] | |
| Nerve growth factor (NGF) | [119] | |
| Amphiregulin | [120,121] | |
| Chemokines | ||
| CXCL8/IL-8, CCL1/I-309, CCL2/MCP-1, CCL3/MIP-1α, CXCL1/GRO-α, CXCL10/IP-10 | They exert several chemotactic and proinflammatory effects. | [122,123,124] |
| Angiogenic factors | ||
| VEGF-A | The main angiogenic factor released by HLMCs. VEGFs released by macrophages, basophils, and neutrophils contribute to mast cell infiltration in bronchial asthma. |
[56,117,125,126,127,128] |
| Angiopoietins (ANGPT1 and ANGPT2) | ANGPTs are involved in blood vessel formation and are released by HLMCs. | [129,130,131,132] |
| LTC4, LTD4 | Non-canonical angiogenic factors. | [133] |
| Lymphangiogenic factors | ||
| VEGF-C, VEGF-D | The main lymphangiogenic factor released by HLMCs. | [58] |