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

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 Ca(2+)-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.

cAMP Response Element Binding Protein Is Required for Differentiation of Respiratory Epithelium during Murine Development

“…Our microarray analysis and qPCR data at E17.5 indicate that with the exception of Sftpd , surfactant protein mRNAs are not greatly affected by a loss of Creb1. Sftpd, together with Sftpa1 and serum mannose-binding protein are members of the calcium-dependent collagenous lectin (collectin) subfamily of mammalian C-type, lectins, and is involved with the immune response to inhaled pathogens and microorganisms [36]. Sftpd mRNA is initially expressed at E16 in mice [37], and its expression is limited to type-II AECs and non-ciliated bronchiolar epithelial cells which are most likely Clara cells [38], [39].…”

Macrophages: Development and Tissue Specialization

“…Additionally, on their luminal surface, type II alveolar epithelial cells express pulmonary surfactant-associated proteins, which bind to immune receptors, such as SIRPα, TLR2, TLR4, and their coreceptors. Moreover, specific surfactant-associated proteins can bind pathogens, apoptotic cells, and allergens to facilitate their neutralization and directly inhibit proinflammatory gene activation (141). As a consequence, alveolar macrophages isolated from mice deficient in surfactant-associated protein D show spontaneous expression of metalloproteinases, as well as oxidant production, resulting in chronic inflammatory alterations (142).…”

Surfactant and its role in the pathobiology of pulmonary infection

“…Human adenovirus can also alter surfactant phospholipid composition [61], whereas Aspergillus fumigatus and Pneumocystis carinii can downregulate SP-B and SP-C protein and mRNA expression [1]. In some studies, pathogens induce expression of collectins [65–67]. …”