Table 1.
The cargos transmitted by Mφ-EVs to recipient cells.
| EVs Source | Precondition of Macrophages | Disease model | Cargos | Mechanism | Reference |
|---|---|---|---|---|---|
| M2-EVs | – | Hepatocellular carcinoma | Integrin αMβ2 (CD11b/CD18) | Promote invasive and metastasis of hepatocellular carcinoma cells via activating MMP‐9 | (24) |
| Mϕ-EVs | Induced by LPS | Acute liver injury | Differentially expressed proteins like IL1rn, Gbp2 | Activate the NLRP3 and NOD-like receptor signaling pathway | (25) |
| M2b-EVs | – | Colitis | CCL1 chemokine | Interact with CCR8 to increase IL-4 expression and Treg percentages | (12) |
| Mϕ-EVs | Treated with endotoxin and nigericin | Autoimmune diseases | The immune response-related proteins | Activate NF-κB signaling pathway | (26) |
| TAM-EVs | Reprogramed glioblastoma-derived EVs | Glioblastoma | Arginase-1 | Promote tumor growth | (27) |
| Mϕ-EVs | Stimulated with angiotensin II | Bleomycin -induced lung fibrosis | Angiotensin II type 1 receptor | Activate TGF-β/smad2/3 pathway | (28) |
| Mϕ-EVs | Exposed to cigarette smoke condensate | HIV-1 | Catalase | Protect U937 cells from oxidative stress and HIV-1 replication | (29) |
| Mϕ-EVs | Exposed to silica | Silicosis | BIP, XBP1s and P‐eIF2α | Induce endoplasmic reticulum stress | (30) |
| Mϕ-EVs | High glucose–treated | Diabetic nephropathy | TGF-β1 mRNA | Activate TGF-β1/Smad3 signaling pathways | (31) |
| Mϕ-EVs | Oxidized LDL-stimulated | AS | EVs transfer | Attenuate the growth and tube formation of endothelial cells | (32) |
| Mϕ-EVs | Treated with Shiga toxin 2a toxoids | Cells death | Globotriaosylceramide (Gb3), IL-1β and IL-8 mRNAs | Activate stress-associated MAPKs and induce ER stress in Gb3-expressing cells | (9) |
| Mϕ-EVs | – | – | Integrin β1 | Promote internalization of integrin β1 in primary HUVECs, make the internalized integrin β1 accumulate in the perinuclear region and not recycled back to the plasma membrane. | (33) |
| Mϕ-EVs | – | Breast adenocarcinoma | Human a disintegrin and metalloproteinase 15 | Enhance binding affinity for integrin αvβ3 in an RGD-dependent manner and suppress vitronectin- and fibronectin-induced cell adhesion, growth, and migration | (34) |
| Mϕ-EVs | Treated with interferon-α or not | Viral infection | Differentially expressed proteins | Be involved in two of the top biological process categories: “Defense response to virus” and “Type I interferon signaling pathway” | (35) |
| Mϕ-EVs | Exposed to silica | Silicosis | SPP1 protein | Phagocytosed by fibroblasts and generate corresponding myofibroblasts | (36) |
| Mϕ-EVs | – | – | Leukotriene B(4) | Produce chemotactic eicosanoids and induced granulocyte migration in the present of Ca (2+)-ionophore and arachidonic acid | (37) |
| Mϕ-EVs | Exposed or not to either LPS or to stationary phase Leishmania mexicana promastigotes | Parasite infection (Leishmania) | Mexicana surface protease GP63 | Induce signaling molecules and transcription factors in naive macrophages | (38) |
| Mϕ-EVs | Exposed to calcium oxalate monohydrate crystals | Kidney stone disease | L-plastin, coronin-like protein, pyruvate kinase, actin-related protein 3, HSP90β, and vimentin | Activate inflammasome, promote monocyte and T-cell migration, monocyte activation and macrophage phagocytic activity | (39) |
| Mϕ-EVs | – | Inflammation brain | Brain derived neurotrophic factor | Interact with brain microvessel endothelial cells via the integrin LFA-1 and ICAM-1, the carbohydrate-binding C-type lectin receptors | (40) |
| Mϕ-EVs | Stimulated with angiotensin II | Hypertension | ICAM-1 and PAI-1, miR-17 | Increase the expression of ICAM1 and PAI-1 in human coronary artery endothelial cells | (41) |
| Mϕ-EVs | Mock-infected or infected with the macrophage-tropic HIV-1 BaL strain | HIV | 48 miRNAs (e.g., miR-29a, miR-150) | Unclear | (42) |
| M2a-EVs, M2b-EVs, M2c-EVs | – | – | MRNA of Il1b、CCL2、CCL7、CCL3, Pf4 | Affect the TLR, TNF, NLR, and NF-κB signaling pathways in recipient cells | (43) |
| M2-EVs | – | Lung cancer | AGAP2-AS1 | Strengthen the radioresistance of radioresistant lung cancer cells via upregulating NOTCH2 and downregulating miR-296 | (44) |
| M2-EVs | – | Pancreatic cancer | LncRNA SBF2-AS1 | Suppress tumorigenic ability of pancreatic cancer via repressing miR-122-5p and upregulating XIAP | (45) |
| M2-EVs | – | Hypertrophic scar | LncRNA-ASLNCS5088 | Modulate glutaminases expression in fibroblasts via targeting miR-200c-3p | (46) |
| M1-EVs | – | Inflammatory bowel disease | MiR-21a-5p | Decrease E-cadherin expression and excessively activate ILC2 via promoting GATA-3 | (47) |
| M1-EVs | – | Myocardial infarction | MiR-155 | Suppress Sirt1/AMPKα2-endothelial nitric oxide synthase and RAC1-PAK2 signaling pathways through targeting RAC1, PAK2, Sirt1, and AMPKα2 | (48) |
| M2-EVs | Treated with IL-4- | AS | MiR-99a/146b/378a | Target NF-κB and TNF-α signaling pathways to suppress inflammation | (49) |
| Mϕ-EVs | – | Idiopathic pulmonary fibrosis | MiR-142-3p | Decrease the expression of TGFβ-R1 and profibrotic genes in alveolar epithelial cells and lung fibroblasts | (50) |
| Mϕ-EVs | Induced by LPS | Inflammation | MiR-146a、miR-146b, miR -21-3p | Secrete various chemokines and cytokines, activate Immune signaling pathways | (51) |
| Mϕ-EVs | Induced by nicotine | AS | MiR-21-3p | Promote vascular smooth muscle cells proliferation and migration through targeting PTEN | (52) |
| Mϕ-EVs | Stimulated by oxidized low-density lipoprotein | AS | MiR-146a | Increase the release of reactive oxygen species ROS and neutrophil extracellular traps NETs via targeting SOD2 | (53) |
| Mϕ-EVs | Induced by deoxycholic acid | Intestinal metaplasia | MiR-30a-5p | Promote the CDX2 expression and suppressed the proliferation of human gastric epithelial cells by targeting FOXD1 | (54) |
| Mϕ-EVs | Induced by LPS | Hepatic fibrosis | MiR-103-3p | Target KLF4 to promote the proliferation and activation of hepatic stellate cells | (55) |
| Mϕ-EVs | Stimulated by Treponema pallidum | Syphilis | MiR-146a-5p | Suppress monocyte transendothelial migration and endothelial permeability via targeting JAM-C | (56) |
| M2-EVs | – | Fracture | MiR-5106 | Induce bone mesenchymal stem cells towards osteoblastic fate by targeting salt-inducible kinase 2 and 3 | (57) |
| Diabetic-Mϕ-EVs | – | Diabetic fracture | MiR-144-5p | Inhibit bone mesenchymal stem cells osteogenesis differentiation by targeting Smad1 | (58) |
| Mϕ-EVs | High glucose–treated | Type 2 diabetes | MiR-210 | Bind with mRNA sequences of NDUFA4 gene to impair glucose uptake and mitochondrial complex IV activity | (59) |
| Mϕ-EVs | – | Spontaneous abortion | MiR-153-3p | Suppress the proliferation and migration of trophoblast cells through the IDO/STAT3 pathway. | (60) |
| M2-EVs | – | Pulmonary fibrosis | MiR-328 | Enhance pulmonary interstitial fibroblast proliferation by targeting FAM13A | (61) |
| M1-EVs | Hypoxia/serum deprivation-induced | Myocardial infarction | MiR-222 | Promote BMSCs apoptosis by targeting Bcl-2 | (62) |
| Mϕ-EVs | – | Ischemia-reperfusion injury | MiR-148a | Suppress the expression of thioredoxin-interacting protein and inactivate the TLR4/NF-κB/NLRP3 signaling pathway | (63) |
| Mϕ-EVs | Stimulated by hypoxia-reoxygenation | Ischemia-reperfusion injury | MiR-29a | Promote inflammatory cytokines secretion and cardiomyocyte pyroptosis by targeting MCL-1 | (64) |
| Mϕ-EVs | – | Type 2 diabetes | MiR-29a | Induce insulin resistance through targeting PPARγ signaling | (65) |
| M1-EVs | – | Carotid artery injuries | MiR-222 | Target CDKN1B and CDKN1C to promote vascular smooth muscle cell proliferation and migration | (66) |
| M2-EVs | – | Acute myocardial infarction | MiR-1271-5p | Decrease cardiomyocyte apoptosis via decreasing SOX6 expression | (67) |
| Mϕ-EVs | Activated by Toll-like receptor 3 | Hepatitis C virus infection | MiR-29 | Induce the expression of IFN-α- and IFN-stimulated genes (ISGs, MxA, OAS-1, and OAS-2) in human hepatic cells | (68) |
| M1-EVs | – | Breast cancer | MiR-130, MiR-33 | Perform anti-tumor effect by polarizing Mϕ from M2 to M1 phenotype | (69) |
| M2-EVs | – | Asthma | MiR-370 | Reduce cell apoptosis, relive inflammation in vitro and in vivo through suppressing the FGF1/MAPK/STAT1 axis | (70) |
MMP-9, Matrix metalloproteinase 9; NLRP3, Nod-like receptor protein 3; NF-κB, Nuclear factor kappa-light-chain-enhancer of activated B cells; TGF-β, Transform growth factor-β; Smad2/3, Small mothers against decapentaplegic 2/3; MAPK, Mitogen-activated protein kinases; ER, Endoplasmic reticulum; HUVECs, Human umbilical vein endothelial cells; LFA-1, Lymphocyte function-associated antigen 1; ICAM-1, Intercellular adhesion molecule 1; PAI-1, Plasminogen activator inhibitor-1; TLR, Toll-like receptors; TNF, Tumor necrosis factor; NLR, NOD-like receptor; RAC1, RAS-related C3 botulinus toxin substrate 1; PAK2, p21-activated kinase 2; Sirt1, Sirtuin 1; AMPKα2, Adenosine monophosphate-activated protein kinas alpha 2; AS, Atherosclerosis; PTEN, Phosphatase and tensin homolog; ROS, Reactive oxygen species; NETs, Neutrophil extracellular traps; SOD2, Superoxide dismutase 2; CDX2, Caudal-related homeobox transcription factor 2; FOXD1, Forkhead Box D1; KLF4, Krüppel-like factor 4; JAM-C, Junctional adhesion molecule C; NDUFA4, NADH dehydrogenase ubiquinone 1 alpha subcomplex 4; IDO, Indoleamine 2,3-dioxygenase; STAT3, Signal Transducers and Activators of Transcription 3; FAM13A, Family with sequence similarity 13, member A; Bcl-2, B-cell lymphoma -2; MCL-1, Myeloid cell leukemia-1; PPARγ, Peroxisome proliferator-activated receptor gamma; CDKN1B, Cyclin Dependent Kinase Inhibitor 1B; CDKN1C, Cyclin Dependent Kinase Inhibitor 1C; SOX6, Sox family transcription factors 6; FGF1, Fibroblast growth factor 1.