Surfactant protein D inhibits TNF-α production by macrophages and dendritic cells in mice

Background

Surfactant protein (SP) D shares target cells with the proinflammatory cytokine TNF-α, an important autocrine stimulator of dendritic cells and macrophages in the airways.

Objective

We sought to study the mechanisms by which TNF-α 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-α, 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-α release and cell influx. SP-D–deficient mice had constitutively high numbers of alveolar mononuclear cells expressing TNF-α, 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-α 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-α on macrophages and dendritic cells, at least partly, by inhibiting production of this cytokine.

Key words: TNF, SP-D, dendritic cell, mouse model, airway inflammation

Abbreviations used: BAL, Bronchoalveolar lavage, SCF, Stem cell factor, SP, Surfactant protein