Autocrine GABA signaling distinctively regulates phenotypic activation of mouse pulmonary macrophages.

In response to micro-environmental cues such as microbial infections or T-helper 1 and 2 (TH 1 and TH 2) cytokines, macrophages (Mϕs) develop into M1- or M2-like phenotypes. Phenotypic polarization/activation of Mϕs are also essentially regulated by autocrine signals. Type-A γ-aminobutyric acid receptor (GABAA R)-mediated autocrine signaling is critical for phenotypic differentiation and transformation of various cell types. The present study explored whether GABAA R signaling regulates lung Mϕ (LMϕ) phenotypic activation under M1/TH 1 and M2/TH 2 environments. Results showed that GABAA R subunits were expressed by primary LMϕ of mice and the mouse Mϕ cell line RAW264.7. The expression levels of GABAA R subunits in mouse LMϕs and RAW264.7 cells decreased or increased concurrently with classical (M1) or alternative (M2) activation, respectively. Moreover, activation or blockade of GABAA Rs distinctively influenced the phenotypic characteristics of Mϕ. These results suggested that microenvironments leading to LMϕ phenotypic polarization concurrently modulates autocrine GABA signaling and its role in Mϕ activation.