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

László Hortobágyi, Sonja Kierstein, Kateryna Krytska, Xiaoping Zhu, Anuk M. Das, Francis R Poulain, Angela Franciska Haczku

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)521-528
Number of pages8
JournalJournal of Allergy and Clinical Immunology
Volume122
Issue number3
DOIs
StatePublished - Sep 2008

Keywords

  • airway inflammation
  • dendritic cell
  • mouse model
  • SP-D
  • TNF

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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