Table 2 Selected in vitro biological activities of AAT.
From: Expanding the Clinical Indications for α1-Antitrypsin Therapy
In vitro assay | Cellular targets | Source and concentration | Outcomes | Reference |
|---|---|---|---|---|
Cell function | ||||
Glucose-stimulated insulin secretion | Mouse islets | Aralast, 0.25–0.5 mg/mL | Cytokine-dampened insulin release restored | |
Human islets | Aralast, 0.5 mg/mL | Impure islet culture insulin release improved | ||
β-cell lines | Prolastin, 0.125-1 mg/mL | Insulin release improved | ||
Collagen I production during wound healing | Skin fibroblasts | Human AAT (Calbiochem), 0.1 ng/mL | Production increased | |
Cell survival | ||||
Proinflammatory cytokine toxicity | Primary mouse islets | Aralast, 0.25–0.5 mg/mL | LDH release diminished | |
Rat INS-1 cell line | Prolastin, 0.5 mg/mL | Cell death reduced | ||
β-cell-specific toxin | Murine MIN-6 cell line | Prolastin, 0.5 mg/mL | Apoptosis reduced | |
(streptozotocin) | ||||
Caspase-3-induced apoptosis | Primary lung alveolar endothelial cells | hAAT (Calbiochem), 0.05 mg/mL | Apoptosis reduced | |
LPS and ischemia-induced injury | Adult cardiac myocyte cell line HL-1 | Aralast, 4.0 mg/mL | Cell death reduced | |
Immune cell cytokine production | ||||
LPS stimulation | Human PBMC | Prolastin, 0.5 mg/mL | Reduced proinflammatory cytokine release | |
Heat-inactivated S. epi. stimulation | Human PBMC | Aralast, 8.0 mg/mL | Reduced proinflammatory cytokine release | |
Steady-state | Nonstimulated murine B cells | Prolastin, 0.5 mg/mL | Steady-state BAFF production decreased | |
LPS stimulation | Human neutrophils | Human neuronal cell line-derived recombinant hAAT 0.5 mg/mL; prolastin, 0.25 mg/mL | Reduced TNF-α release, | |
Mixed lymphocyte reaction | Human PBMC | Aralast, 0.1–0.5 mg/mL | Reduced IL-32 | |
Mixed lymphocyte-DC reaction | Murine OT-II T cells and OVA-loaded DC | Aralast, 0.5 mg/mL | Reduced IL-6, elevated IL-2 and elevated IL-10 | |
Immune cells not directly targeted by AAT | ||||
In vitro immunization | Mouse splenocytes | Prolastin, 0.5 mg/mL | Intact T-cell clumping, proliferation, response to IL-2 and IFNγ release | |
Concanavalin A stimulation | Mouse splenocytes | Aralast, 0.5 mg/mL | ||
CD3/CD28 stimulation | Purified mouse T cells | Aralast, 0.5 mg/mL |