Glycyrrhizin inhibits neutrophil-associated generation of alternatively activated macrophages

Patients with severe burn injuries are extremely susceptible to infection, and the host's antibacterial responses are frequently suppressed by alternatively activated macrophages (M2Mϕ), commonly demonstrated in these patients. An immunosuppressive subset of neutrophils (PMN-II), demonstrated in the peripheral blood of thermally injured patients, has been described as an inducer of M2Mϕ. In the present studies, the inhibitory effect of glycyrrhizin (GL) on M2Mϕ generation stimulated by PMN-II was examined. M2Mϕ were generated from resident Mϕ (R-Mϕ, lower chamber) after cultivation with PMN-II (upper chamber) in a dual-chamber transwell. However, M2Mϕ were not generated from R-Mϕ when the same transwell cultures were performed in the presence of GL. M2Mϕ were not generated from R-Mϕ after cultivation with PMN-II previously treated with GL, while R-Mϕ previously treated with GL converted to M2Mϕ after they were cultured with PMN-II in transwells. Interleukin-10 and CCL2 released from PMN-II were shown to be effector molecules responsible for the generation of M2Mϕ. However, these soluble factors were not produced by PMN-II treated with GL. These results indicate that GL inhibits PMN-II-stimulated M2Mϕ generation through the inhibition of CCL2/interleukin-10 production by PMN-II.