Table 1. Cytokines, chemokines, and growth factor production by uterine natural killer cells.
Publication | Cytokines, chemokines, and growth factors detected | Cell preparation | Gestational age | Conditions |
---|---|---|---|---|
El Costa et al. 45 | IFNγ, TNFα, MIP-1α, MIP-1β, GM-CSF | MACS-negative selection, 96% CD3−CD56+ | 8–12 weeks | Engagement of NKp30 (but not
NKp46) |
Higuma-Myojo
et al. 79 |
TGF, minor populations of CD56+ cells producing other
cytokines |
Ficoll, flow cytometry | 6–12 weeks | Mononuclear cells stimulated with
PMA/ionomycin/brefeldin 4 hours, flow cytometry |
Lash et al. 38 | Ang1, Ang2, PDGF-BB (low), KGF (low), ICAM-1 (low),
VEGF-C, PlGF, TGFβ1 |
MACS-positive selection, >95% CD56+ | 8–10 weeks, 12–14
weeks |
No stimulation, Fastquant, ELISA |
Lash et al. 39 | IL-1β, IL-4, IL-6, IL-8, IL-10, IL-13, GM-CSF, IFNγ,
RANTES, TNFα |
MACS-positive selection >95% CD56+ | 8–10 weeks, 12–14
weeks |
No stimulation, Fastquant, ELISA |
Hanna et al. 66 | CXCL8 (IL-8), CXCL10 (IP-10), CCL5 (RANTES), CCL22,
MIP-1α, MIP-1β, PlGF, VEGF-A, VEGF-B, VEGF-C |
Flow cytometry cell sorting, >99% CD56
bright
CD16−CD3− |
First trimester | IL-15 72 hours |
Sotnikova et al. 62 | IFNγ | Dynabeads-positive selection | 7–10 weeks | Incubation with autologous
cytotrophoblast |
Engert et al. 80 | GRO, MCP1, I-309, RANTES, IL-8, IL-1β, EGF, VEGF,
TPO, M-CSF, ENA, oncostatin M, IL-10, GROα, angiogenin, IL-1α, IL-4, IL-12p40p70, IFNγ, SCF, SDF-1, MCP-2 (detected in >50% samples) |
MACS, >90% pure | 7–8 weeks | No stimulation, protein array |
Saito et al. 81 | G-CSF, GM-CSF, M-CSF, TNFα, IFNγ, LIF | Flow cytometry sorting | 7–9 weeks | No stimulation |
Fraser et al. 82 | CXCL16, HB-EGF, HGF, IL-1β, IL-8, TGFβ1, UPA, TIMP-1 | MACS-positive selection, 93.6 ± 1.3% CD56
+,
80 ± 4% viability after 24 hours |
9.1–13.7 weeks | IL-15, SCF |
Wallace et al. 83 | IL-6, IL-8, CXCL10 | MagCellect-negative selection, CD56+ 95.7 ±
0.92%, viability after 6 hours 84.6 ± 2.8% |
8–14 weeks | IL-15, SCF |
Wallace et al. 84 | Angiogenin, sIL2-R, endostatin, PlGF, IL-1RA, MIG, MIP-
1α, MIP-1β, RANTES |
MACS-positive selection, 93.6 ± 1.3% CD56+ | 9–14 weeks | IL-15, SCF |
Wallace et al. 85 | TNFα, CXCL10, IFNγ, IL-8, PlGF (mRNA) | MagCellect-negative selection, CD56+ 95.7 ±
0.92%, viability after 6 hours 84.6 ± 2.8% |
9–14 weeks | IL-15, SCF |
Kennedy et al. 63 | GM-CSF, CCL3, CCL1, XCL1 | Flow cytometry and intracellular cytokine
detection; or MACS positive selection and ELISA |
First trimester | Activation of KIR2DS4 |
Chen et al. 86 | Angiogenin, bFGF, VEGF-A, VEGFR, IL-1α | MACS-positive selection, 91.3%
CD16−CD56+ |
LH+7 non-pregnant
endometrium |
|
Fu et al. 65 | Pleiotrophin, osteopontin, osteoglycin | Ficoll, MACS-negative selection | First trimester | Co-culture with EVT |
Ang, angiopoetin; bFGF, basic fibroblast growth factor; CCL, C-C motif chemokine; EGF, epidermal growth factor; ELISA, enzyme-
linked immunosorbent assay; ENA, epithelial neutrophil-activating protein; EVT, extravillous trophoblast; G-CSF, granulocyte colony-stimulating factor; GM-CSF, granulocyte-macrophage colony-stimulating factor; GRO, growth-regulated oncogene; HB-EGF, heparin-binding epidermal growth factor; HGF, hepatocyte growth factor; ICAM-1, intercellular adhesion molecule 1; IFN, interferon; IL, interleukin; KGF, keratinocyte growth factor; LIF, leukocyte inhibitory factor; MACS, magnetic-activated cell sorting; MCP, monocyte chemotactic protein; M-CSF, macrophage colony-stimulating factor; MIG, monokine induced by interferon-gamma; MIP, macrophage inflammatory protein; PDGF-BB, platelet-derived growth factor beta; PlGF, placental growth factor; RANTES, regulated upon activation, normal T cell expressed, and secreted; SCF, stem cell factor; SDF-1, stromal cell-derived factor 1; sIL2-R, soluble interleukin-2 receptor; TGF, transforming growth factor; TIMP-1, tissue inhibitor of metalloproteinase 1; TNFα, tumor necrosis factor alpha; TPO, thrombopoietin; UPA, urokinase-type plasminogen activator; VEGF, vascular endothelial growth factor; VEGFR, vascular endothelial growth factor receptor.