Human monocytes but not dendritic cells are killed by blocking of autocrine cyclooxygenase activity.
Dendritic cells (DCs), in peripheral tissues, derive mostly from blood precursors that differentiate into DCs under the influence of the local microenvironment. Monocytes constitute the main known DC precursors in blood and their infiltration into tissues is up-regulated during inflammation. During this process, the local production of mediators, like prostaglandins (PGs), influence significantly DC differentiation and function. In the present paper we show that treatment of blood adherent mononuclear cells with 10microM indomethacin, a dose achieved in human therapeutic settings, causes monocytes' progressive death but does not affect DCs viability or cell surface phenotype. This resistance of DCs was observed both for cells differentiated in vitro from blood monocytes and for a population with DCs characteristics already present in blood. This phenomenon could affect the local balance of antigen-presenting cells, influence the induction and pattern of immune responses developed under the treatment with non-steroidal anti-inflammatory drugs and, therefore, deserves further investigation.
Oliveira
Bruno L
BL
Laboratory of Tumor Immunology, Department of Immunology, University of São Paulo, São Paulo, Brazil.
Cavalcanti
Clara M
CM
Azevedo
Ana Paula S
AP
Tomiyoshi
Márcio Y
MY
Bergami-Santos
Patrícia C
PC
Barbuto
José Alexandre M
JA
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D016923:Cell Death; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D003713:Dendritic Cells / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology*; D009000:Monocytes / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D014409:Tumor Necrosis Factor-alpha; D011451:Prostaglandin-Endoperoxide Synthases; D007213:Indomethacin