SP-D and regulation of the pulmonary innate immune system in allergic airway changes

Research output: Contribution to journalReview article

22 Citations (Scopus)

Abstract

The airway mucosal surfaces are constantly exposed to inhaled particles that can be potentially toxic, infectious or allergenic and should elicit inflammatory changes. The proximal and distal air spaces, however, are normally infection and inflammation free due to a specialized interplay between cellular and molecular components of the pulmonary innate immune system. Surfactant protein D (SP-D) is an epithelial-cell-derived immune modulator that belongs to the small family of structurally related Ca2+-dependent C-type collagen-like lectins. While collectins can be detected in mucosal surfaces of various organs, SP-A and SP-D (the 'lung collectins') are constitutively expressed in the lung at high concentrations. Both proteins are considered important players of the pulmonary immune responses. Under normal conditions however, SP-A-/- mice display no pathological features in the lung. SP-D-/- mice, on the other hand, show chronic inflammatory alterations indicating a special importance of this molecule in regulating immune homeostasis and the function of the innate immune cells. Recent studies in our laboratory and others implied significant associations between changes in SP-D levels and the presence of airway inflammation both in animal models and patients raising a potential usefulness of this molecule as a disease biomarker. Research on wild-type and mutant recombinant molecules in vivo and in vitro showed that SP-D binds carbohydrates, lipids and nucleic acids with a broad spectrum specificity and initiates phagocytosis of inhaled pathogens as well as apoptotic cells. Investigations on gene-deficient and conditional over expressor mice in addition, provided evidence that SP-D directly modulates macrophage and dendritic cell function as well as T cell-dependent inflammatory events. Thus, SP-D has a unique, dual functional capacity to induce pathogen elimination on the one hand and control of pro-inflammatory mechanisms on the other, suggesting a potential suitability for therapeutic prevention and treatment of chronic airway inflammation without compromising the host defence function of the airways. This paper will review recent findings on the mechanisms of immune-protective function of SP-D in the lung.

Original languageEnglish (US)
Pages (from-to)547-562
Number of pages16
JournalClinical and Experimental Allergy
Volume40
Issue number4
DOIs
StatePublished - Apr 2010
Externally publishedYes

Fingerprint

Pulmonary Surfactant-Associated Protein D
Immune System
Lung
Collectins
Inflammation
Pulmonary Surfactant-Associated Protein A
Poisons
Phagocytosis
Lectins
Dendritic Cells
Nucleic Acids
Homeostasis
Collagen
Animal Models
Biomarkers
Epithelial Cells
Macrophages
Air
Carbohydrates
T-Lymphocytes

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

SP-D and regulation of the pulmonary innate immune system in allergic airway changes. / Forbes, L. R.; Haczku, Angela Franciska.

In: Clinical and Experimental Allergy, Vol. 40, No. 4, 04.2010, p. 547-562.

Research output: Contribution to journalReview article

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