title: Stimulation of Ly-6G on neutrophils in LPS-primed mice induces platelet-activating factor (PAF)-mediated anaphylaxis-like shock.
abstract: Previously, two anti-Ly-6G mAb-RB6-8C5 and 1A8-have been used to deplete neutrophils in mice and to clarify their involvement in immune responses. During the course of experiments on neutrophil depletion, we noticed that i.v. injection of RB6-8C5 or 1A8 induced anaphylaxis-like shock in mice pretreated i.v. with LPS. Signs of shock, such as hypothermia, appeared within a few minutes, and the mice died of shock within 20 min of the antibody injection. In vivo experiments, including depletion of various cell types, indicated that neutrophils and macrophages (but not platelets, basophils, or mast cells) are involved in the shock. Experiments using various drugs and gene-targeted mice demonstrated that PAF is the central mediator of the shock. Optimal LPS priming required at least 1 h, and the priming was associated with neutrophil accumulation within pulmonary and hepatic blood vessels. Consistently, following 1A8 injection into LPS-pretreated mice, the mRNA for LysoPAFAT (a PAF biosynthetic enzyme) was markedly up-regulated in neutrophils accumulated in the lung but not in macrophages. These results suggest that (1) stimulation of Ly-6G on LPS-primed neutrophils induces PAF-mediated anaphylaxis-like shock in mice, (2) neutrophils are primed by LPS during and/or after their accumulation in lung and liver to rapidly induce LysoPAFAT, and (3) macrophages may play a pivotal role in the priming phase and/or in the challenge phase by unknown mechanisms. These findings may be related to adult respiratory distress syndrome, although the natural ligand for Ly-6G remains to be identified.
authors: Department of Oral Biology, Tohoku University Graduate School of Dentistry, 4-1 Seiryo-machi, Aoba-ku, Sendai, Japan. yukinori-tanaka@dent.tohoku.ac.jp
authors: Yukinori
authors: Y
authors: Tanaka
authors: Yasuhiro
authors: Y
authors: Nagai
authors: Toshinobu
authors: T
authors: Kuroishi
authors: Yasuo
authors: Y
authors: Endo
authors: Shunji
authors: S
authors: Sugawara
mesh_terms: D000707:Anaphylaxis / Q000276:immunology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology; D000950:Antigens, Ly / Q000276:immunology*; D047589:Leukocyte Reduction Procedures; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000276:immunology*; D008099:Liver / Q000276:immunology / Q000473:pathology; D008168:Lung / Q000276:immunology / Q000473:pathology; D008264:Macrophages / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020556:Neutrophil Infiltration / Q000276:immunology; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism; D010972:Platelet Activating Factor / Q000276:immunology / Q000378:metabolism*; D013997:Time Factors
chemical_list: D000911:Antibodies, Monoclonal; D000950:Antigens, Ly; D008070:Lipopolysaccharides; C480309:Ly6G antigen, mouse; D010972:Platelet Activating Factor