title: Role of biphasic changes in splenic dendritic cell activity in a mouse model of multiple organ dysfunction syndrome.
abstract: To analyze the changes in splenic dendritic cell (DC) activity and serum cytokine levels during the progression of multiple organ dysfunction syndrome (MODS). A C57BL/6 mouse model of MODS was established by intraperitoneal injection of zymosan. Immunohistochemistry and flow cytometry were used to detect expression of I-A(b) (MHC-II molecules of mice) as well as co-stimulatory and co-inhibitory molecules in spleen and DC surface. The levels of various cytokines in serum and spleen tissue were analyzed 6 h, 12 h, 24 h, 48 h, 5 d and 12 d after injury. Death occurred at 24-48 h and 10-12 d after injury. The expression of I-A(b) and CD86 in spleen tissue and on DCs increased 6-12 h after injury, followed by gradual reduction and at 12 d. The inhibitory molecule, PD-L1, was expressed on normal DCs, but expression of PD-1 was undetectable. PD-L1 and PD-1 expression increased and remained high at 5 d and 12 d after injury. In addition, TNF and IL-1 levels increased 6-12 h after injury; HMGB1 and IL-10 levels increased 24 h and 5 d after injury, respectively. In contrast, IL-2 and IL-12 decreased with disease progression. At 12 d after injury, proinflammatory and anti-inflammatory cytokine levels remained high, while IL-2 and IL-12 were significantly reduced. IL-10 and IL-12 changes in spleen were consistent with those in serum. MODS progression was characterized by changes in splenic DC activity as well as altered serum pro-inflammatory and anti-inflammatory cytokine levels, suggesting early immune activation and predominant immune tolerance at the late stage.
authors.affiliation: Department of Pathology, The First Affiliated Hospital of General Hospital of PLA Beijing 100048, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Lv
authors.affiliation: Department of Pathology, The First Affiliated Hospital of General Hospital of PLA Beijing 100048, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Pathology, The First Affiliated Hospital of General Hospital of PLA Beijing 100048, China.
authors.forename: Min
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Department of Pathology, The First Affiliated Hospital of General Hospital of PLA Beijing 100048, China.
authors.forename: Yiduo
authors.initials: Y
authors.lastname: Jin
authors.affiliation: Department of Pathology, The First Affiliated Hospital of General Hospital of PLA Beijing 100048, China.
authors.forename: Jiangyang
authors.initials: J
authors.lastname: Lu
mesh_terms: D000818:Animals; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D005434:Flow Cytometry; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009102:Multiple Organ Failure / Q000276:immunology* / Q000473:pathology; D013154:Spleen / Q000276:immunology* / Q000378:metabolism
chemical_list: D016207:Cytokines
keywords: MODS; Splenic dendritic cell; immunohistochemical staining