Prostaglandins D-2 and E-2 have opposite effects on alveolar macrophages infected with Histoplasma capsulatum

Author(s)

Pereira, Priscilla A. T. ^[1] ; Assis, Patricia A. ^[1] ; Prado, Morgana K. B. ^[1] ; Ramos, Simone G. ^[2] ; Aronoff, David M. ^[3] ; de Paula-Silva, Francisco W. G. ^[1] ; Sorgi, Carlos A. ^[1] ; Faccioli, Lucia H. ^[1]

Affiliation

^[1] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Anal Clin Toxicol & Bromatol, BR-14040903 Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Pathol, BR-14040903 Ribeirao Preto, SP - Brazil

^[3] Vanderbilt Univ, Med Ctr, Dept Med, Div Infect Dis, Nashville, TN 37232 - USA

• Document type: Journal article
• Source: Journal of Lipid Research; v. 59, n. 2, p. 195-206, FEB 2018.
• Web of Science Citations: 5

Abstract

Prostaglandin E2 (PGE(2)) suppresses macrophage effector mechanisms; however, little is known about the function of PGD(2) in infected alveolar macrophages (AMs). Using serum-opsonized Histoplasma capsulatum (Ops-H. capsulatum) in vitro, we demonstrated that AMs produced PGE(2) and PGD(2) in a time-dependent manner, with PGE(2) levels exceeding those of PGD(2) by 48 h postinfection. Comparison of the effects of both exogenous PGs on AMs revealed that PGD(2) increased phagocytosis and killing through the chemoattractant receptor-homologous molecule expressed on Th2 lymphocytes receptor, whereas PGE(2) had opposite effects, through E prostanoid (EP) receptor 2 (EP2)/EP4-dependent mechanisms. Moreover, PGD(2) inhibited phospholipase C-gamma (PLC-gamma) phosphorylation, reduced IL-10 production, and increased leukotriene B4 receptor expression. In contrast, exogenous PGE(2) treatment reduced PLC-gamma phosphorylation, p38 and nuclear factor kappa B activation, TNF-alpha, H2O2, and leukotriene B4, but increased IL-1 beta. production. Using specific compounds to inhibit the synthesis of each PG in vitro and in vivo, we found that endogenous PGD(2) contributed to fungicidal mechanisms and controlled inflammation, whereas endogenous PGE(2) decreased phagocytosis and killing of the fungus and induced inflammation. These findings demonstrate that, although PGD(2) acts as an immunostimulatory mediator to control H. capsulatum infection, PGE(2) has immunosuppressive effects, and the balance between these two PGs may limit collateral immune damage at the expense of microbial containment. (AU)

• FAPESP's process: 09/07169-5 - Lipid mediators as regulators of immune response
• Grantee: Lúcia Helena Faccioli
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 14/07125-6 - New functional aspects of eicosanoids
• Grantee: Lúcia Helena Faccioli
• Support Opportunities: Research Projects - Thematic Grants