Surfactant protein D inhibits TNF-alpha production by macrophages and dendritic cells in mice.
BACKGROUND
Surfactant protein (SP) D shares target cells with the proinflammatory cytokine TNF-alpha, an important autocrine stimulator of dendritic cells and macrophages in the airways.


OBJECTIVE
We sought to study the mechanisms by which TNF-alpha and SP-D can affect cellular components of the pulmonary innate immune system.


METHODS
Cytokine and SP-D protein and mRNA expression was assessed by means of ELISA, Western blotting, and real-time PCR, respectively, by using in vivo models of allergic airway sensitization. Macrophage and dendritic cell phenotypes were analyzed by means of FACS analysis. Maturation of bone marrow-derived dendritic cells was investigated in vitro.


RESULTS
TNF-alpha, elicited either by allergen exposure or pulmonary overexpression, induced SP-D, IL-13, and mononuclear cell influx in the lung. Recombinant IL-13 by itself was also capable of enhancing SP-D in vivo and in vitro, and the SP-D response to allergen challenge was impaired in IL-13-deficient mice. Allergen-induced increase of SP-D in the airways coincided with resolution of TNF-alpha release and cell influx. SP-D-deficient mice had constitutively high numbers of alveolar mononuclear cells expressing TNF-alpha, MHC class II, CD86, and CD11b, characteristics of proinflammatory, myeloid dendritic cells. Recombinant SP-D significantly suppressed all of these molecules in bone marrow-derived dendritic cell cultures.


CONCLUSIONS
TNF-alpha can contribute to enhanced SP-D production in the lung indirectly through inducing IL-13. SP-D, on the other hand, can antagonize the proinflammatory effects of TNF-alpha on macrophages and dendritic cells, at least partly, by inhibiting production of this cytokine.
Department of Medicine, University of Pennsylvania, Philadelphia.
László
L
Hortobágyi
Department of Medicine, University of Pennsylvania, Philadelphia.
Sonja
S
Kierstein
Department of Medicine, University of Pennsylvania, Philadelphia.
Kateryna
K
Krytska
Department of Medicine, University of Pennsylvania, Philadelphia.
Xiaoping
X
Zhu
Centocor, King of Prussia.
Anuk M
AM
Das
Department of Pediatrics, University of California at Davis.
Francis
F
Poulain
Department of Medicine, University of Pennsylvania, Philadelphia.
Angela
A
Haczku
D000818:Animals; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D018793:Interleukin-13 / Q000172:deficiency / Q000276:immunology / Q000378:metabolism*; D008168:Lung / Q000276:immunology; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D037663:Pulmonary Surfactant-Associated Protein D / Q000172:deficiency / Q000276:immunology / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism*
D018793:Interleukin-13; D037663:Pulmonary Surfactant-Associated Protein D; D014409:Tumor Necrosis Factor-alpha