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Leukadherin-1 is a allosteric activator of CD11b/CD18. Leukadherin-1 increases CD11b/CD18-dependent cell adhesion to fibrinogen (EC50 = 4 μM). Leukadherin-1 decreases leukocyte motility and transendothelial migration; reduces inflammation. Leukadherin-1 also activates complement receptor 3 (CR3), and promotes CR3-dependent leukocyte adhesion to fibrinogen-coated surfaces. Leukadherin‐1 pretreatment also reduces secretion of IL‐1β, IL‐6 and TNF by Toll‐like receptor (TLR)‐2 and TLR‐7/8‐stimulated monocytes.
Leukadherin-1 (1 mg/kg; i.p.; twice daily for 14 days) is beneficial in preventing hyperoxia-induced neonatal lung injury, an experimental model of bronchopulmonary dysplasia (BPD).
| Cell Experiment | |
|---|---|
| Cell lines | NK cells |
| Preparation method | NK cell stimuli (where used) were added as follows: (1) Syk inhibitor (1 μM), (2) Leukadherin-1 or dimethylsulphoxide (DMSO) (vector control) (7.5 μM). Shown to induce ∼82% of maximum response with negligible off-target effect, (3) anti-CD210 or isotype control (5 µg/ml), (4) 30-45 min after Leukadherin‐1 NK cells were stimulated with combinations of IL-12 (10 ng/ml), IL-15 (30 ng/ml) or IL-18 (10 ng/ml): either IL-12 + IL-15 or IL-12 + IL-18. Monocytes were stimulated using pam3csk4 (TLR-2 agonist, 300 ng/ml) or R848 (TLR-7/8 agonist, 2 µg/ml). Supernatants were stored at −80ºC for < 1 month before quantification. To exclude non-specific Leukadherin-1-mediated cytotoxicity, cell viability is assessed at 24 h using the CellTitre-Glo reagent. |
| Concentrations | 7.5 μM |
| Incubation time | 30-45 min |
| Animal Experiment | |
|---|---|
| Animal models | Male C57BL/6J (H-2b) and Balb/cJ (H-2d) mice |
| Formulation | cyclosporine |
| Dosages | 1 mg/kg or 2.5 mg/kg |
| Administration | i.v. or i.p. |
| Molecular Weight | 421.49 |
| Formula | C22H15NO4S2 |
| CAS Number | 344897-95-6 |
| Solubility (25°C) | DMSO 4 mg/mL (with gentle warming) |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
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