Figure 3. Only benzodiazepines that activate α1 subunit containing GABAA receptors affect macrophage function.
A, Alveolar macrophages, purified from C57BL/6 mice, were incubated with vehicle (V), diazepam (D) (10 μM), muscimol (M) (100 μM) or L-838-417 (L) (567nM; an equivalent Ki multiple to diazepam6), and lipopolysaccharide (LPS) (100 ng ml−1), tumor necrosis factor (TNF)-α release was measured by ELISA (n = 3–7 per group). B, Change in phagocytosis of phrodo-labeled Staphylococcus aureus (n = 3–6 per group) assessed at 1 hr with diazepam, GABA (100 μM), or L. C, Alveolar macrophages were incubated with V, D, bicuculline (B), and B and D (B+D), or L, and killing of Streptococcus pneumoniae was assessed by counting bacterial colonies (n = 3 wells/group). Cytoplasmic pH was measured by BCECF probe in untreated (D), interleukin-4–treated (E), and LPS-treated alveolar macrophage (F) (n = 10 wells per treatment). G, H+ concentration correlates with expression of γ2 subunit expression as assessed by geomean.