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Am J Pathol ; 181(2): 535-47, 2012 Aug.
Article in English | MEDLINE | ID: mdl-22677422

ABSTRACT

Inflammatory mediators from peripheral tissues may control dendritic cell (DC) development in the bone marrow. In this study, DCs (CD11c(+) cells) differentiated from the bone marrow of mice with inflammation of the airways, or the peritoneal cavity had poor priming ability resulting in reduced, long-lived responses to that antigen in vivo. This indicates enhancement of regulatory mechanisms of immune responses through a peripheral tissue-bone marrow axis. If CD11c(+) cells, expanded from the bone marrow of mice with tissue inflammation were antigen pre-loaded and injected into mice already sensitized to that antigen, then subsequent contact hypersensitivity responses were significantly reduced. The effects of inflammation were imprinted in vivo and were independent of in vitro culture conditions for DC differentiation. The effect of tissue inflammation on the bone marrow DC precursors was not detected in mice treated subcutaneously with slow-release indomethacin pellets, suggesting a role for prostanoids, including prostaglandin E(2), in differentiation of regulatory CD11c(+) cells from bone marrow. Our study represents an important homeostatic process with potential for therapeutic use in the future.


Subject(s)
Bone Marrow Cells/immunology , Bone Marrow Cells/pathology , Dendritic Cells/immunology , Homeostasis/immunology , Inflammation/pathology , Lung/pathology , Peritoneal Cavity/pathology , Alum Compounds , Animals , B7-2 Antigen/metabolism , Bone Marrow Cells/drug effects , CD11c Antigen/metabolism , Cell Differentiation/drug effects , Cell Movement/immunology , Cross-Priming/immunology , Dendritic Cells/drug effects , Dendritic Cells/enzymology , Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology , Haptens/immunology , Homeostasis/drug effects , Hypersensitivity/complications , Hypersensitivity/immunology , Hypersensitivity/pathology , Immunization , Indomethacin/pharmacology , Inflammation/complications , Inflammation/immunology , Interleukin-4/pharmacology , Lung/drug effects , Lung/immunology , Lung Diseases/complications , Lung Diseases/immunology , Lung Diseases/pathology , Lymph Nodes/drug effects , Lymph Nodes/pathology , Membrane Proteins/pharmacology , Mice , Mice, Inbred BALB C , Myelopoiesis/drug effects , Ovalbumin/immunology
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