title: Glycyrrhizin inhibits neutrophil-associated generation of alternatively activated macrophages.
abstract: Patients with severe burn injuries are extremely susceptible to infection, and the host's antibacterial responses are frequently suppressed by alternatively activated macrophages (M2Mphi), 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 M2Mphi. In the present studies, the inhibitory effect of glycyrrhizin (GL) on M2Mphi generation stimulated by PMN-II was examined. M2Mphi were generated from resident Mphi (R-Mphi, lower chamber) after cultivation with PMN-II (upper chamber) in a dual-chamber transwell. However, M2Mphi were not generated from R-Mphi when the same transwell cultures were performed in the presence of GL. M2Mphi were not generated from R-Mphi after cultivation with PMN-II previously treated with GL, while R-Mphi previously treated with GL converted to M2Mphi 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 M2Mphi. However, these soluble factors were not produced by PMN-II treated with GL. These results indicate that GL inhibits PMN-II-stimulated M2Mphi generation through the inhibition of CCL2/interleukin-10 production by PMN-II.
authors.affiliation: Department of Internal Medicine, The University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555-0435, USA.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Yoshida
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Tsuda
authors.forename: Dan
authors.initials: D
authors.lastname: Takeuchi
authors.forename: Makiko
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Richard B
authors.initials: RB
authors.lastname: Pollard
authors.forename: Fujio
authors.initials: F
authors.lastname: Suzuki
mesh_terms: D000818:Animals; D002056:Burns / Q000188:drug therapy / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000096:biosynthesis; D019695:Glycyrrhizic Acid / Q000494:pharmacology*; D006131:Growth Inhibitors / Q000494:pharmacology*; D016753:Interleukin-10 / Q000096:biosynthesis; D008262:Macrophage Activation / Q000502:physiology*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000145:classification / Q000187:drug effects* / Q000502:physiology*
chemical_list: D018932:Chemokine CCL2; D006131:Growth Inhibitors; D016753:Interleukin-10; D019695:Glycyrrhizic Acid