Leukadherin 1 is a allosteric activator of CD11b/CD18. Increases CD11b/CD18-dependent cell adhesion to fibrinogen (EC50 = 4 μM). Decreases leukocyte motility and transendothelial migration; reduces inflammation. Also activates complement receptor 3 (CR3), and promotes CR3-dependent leukocyte adhesion to fibrinogen-coated surfaces.
| 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 4.21 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 |
| Species | Mouse | Rat | Rabbit | Guinea pig | Hamster | Dog |
| Weight (kg) | 0.02 | 0.15 | 1.8 | 0.4 | 0.08 | 10 |
| Body Surface Area (m2) | 0.007 | 0.025 | 0.15 | 0.05 | 0.02 | 0.5 |
| Km factor | 3 | 6 | 12 | 8 | 5 | 20 |
| Animal A (mg/kg) = Animal B (mg/kg) multiplied by | Animal B Km |
| Animal A Km |
For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.
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| Integrin Binding Peptide
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