Effects of Surfactant Protein D (SP-D) on Dendritic Cell Subtypes in the Lung in Mice

Abstract

RATIONALE: In murine models of airway inflammation it was shown that unlike the tolerogenic plasmocytoid dendritic cells, myeloid (bone-marrow derived) dendritic cells are central in promoting the allergic airway response. The role of SP-D in regulating presence of dendritic cell subtypes in the lung is unclear. METHODS: Cytokine and SP-D protein and mRNA expression was assessed by ELISA, Western blot and real-time PCR, respectively, using in vivo models of allergic airway sensitization. Macrophage and dendritic cell phenotypes and intracellular TNFa expression were analyzed by FACS. Maturation of ckit+ bone-marrow derived dendritic cells was investigated in vitro. Migration was studied by PKH26 uptake in vivo. RESULTS: TARC (thymus and activation regulated chemokine, responsible for attracting activated dendritic cells) showed an early upregulation in the airways followed by a resolution after allergen challenge of wild-type mice. SP-D-/- animals however had a constitutive TARC expression in the BAL fluid. Intraperitoneal PKH26 injection revealed a preferential accumulation of phagocytic cells in the lungs of SP-D-/- mice in comparison with wild-type animals. Bronchoalveolar lavage cells of SP-D-/- mice had increased numbers of activated, TNFα- and TARC expressing, myeloid dendritic cells. Recombinant SP-D significantly suppressed MHC class-II, CD86 and CD11b as well as intracellular TNFα in bone marrow-derived (myeloid) dendritic cell cultures in vitro. CONCLUSIONS: Presence of SP-D in the lung is important to prevent constitutive migration and activation of proinflammatory myeloid dendritic cells. Such negative regulation may facilitate resolution of acute inflammatory changes and prevents development of chronic conditions such as asthma.