Surfactant Protein D Reduces Alveolar Macrophage Apoptosis In Vivo

Clark, Howard; Palaniyar, Nades; Strong, Peter; Edmondson, Jess; Hawgood, Samuel

doi:10.4049/jimmunol.169.6.2892

Cited by 144 publications

(142 citation statements)

References 34 publications

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“…As has been shown for C1q and SP-D [3,14], we were able to demonstrate that MBL binds to late apoptotic and necrotic cells. MBL binds only to cells positive both for annexin V and nuclear dyes when induced to apoptosis, as well to cells becoming directly necrotic after heat shock.…”

Section: Discussionsupporting

confidence: 83%

Mannose‐binding lectin engagement with late apoptotic and necrotic cells

et al. 2003

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The serum opsonin mannose-binding lectin (MBL) has been shown to be involved in the handling of apoptotic cells. However, at what stage in the process this happens and whether this mediates activation of complement is unknown. Cells rendered apoptotic or necrotic were incubated with purified MBL/MBL-associated serine protease (MASP) complexes and assessed by flow cytometry and fluorescence microscopy. MBL bound specifically to late apoptotic cells, as well as to apoptotic blebs and to necrotic cells, but not to early apoptotic cells. Binding of MBL could be inhibited by EDTA as well as with an antibody against the CRD region. Addition of C1q, another serum opsonin involved in the handling of apoptotic cells, prior to MBL partly inhibited MBL binding to apoptotic cells and vice versa. MBL/ MASP could initiate deposition of purified complement C4 on the target cells. However, addition of MBL/MASP to whole serum deficient for both C1q and MBL did not enhance deposition of C4, but MBL enhanced phagocytosis of apoptotic cells by macrophages. These results demonstrate that MBL interacts with structures exposed on cells rendered late apoptotic or necrotic and facilitates uptake by macrophages. Thus, MBL may promote noninflammatory sequestration of dying host cells.

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Section: Discussionsupporting

confidence: 83%

Mannose‐binding lectin engagement with late apoptotic and necrotic cells

et al. 2003

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“…8 In both in vitro and in vivo studies, SP-D has been reported to bind to, and mediate the clearance of, apoptotic inflammatory cells by alveolar macrophages. [9][10][11] Studies with SP-D knockout mice have also indicated a role of SP-D in the regulation of surfactant lipid homeostasis. 12 Furthermore, Brinker and colleagues 13 found that human SP-D binds to immature bone marrow-derived dendritic cells (DC) in vitro in a dose-, carbohydrate-and calcium-dependent manner, enhancing the phagocytic uptake of Escherichia coli and the antigen presentation to T cells.…”

Section: Introductionmentioning

confidence: 99%

Pulmonary infections in swine induce altered porcine surfactant protein D expression and localization to dendritic cells in bronchial‐associated lymphoid tissue

Soerensen¹,

Holmskov

Aalbæk³

et al. 2005

Immunology

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SummarySurfactant protein D (SP-D) is a pattern-recognition molecule of the innate immune system that recognizes various microbial surface-specific carbohydrate and lipid patterns. In vitro data has suggested that this binding may lead to increased microbial association with macrophages and dendritic cells. The aim of the present in vivo study was to study the expression of porcine SP-D (pSP-D) in the lung during different pulmonary bacterial infections, and the effect of the routes of infection on this expression was elucidated. Furthermore, the aim was to study the in vivo spatial relationship among pSP-D, pathogens, phagocytic cells and dendritic cells. Lung tissue was collected from experimental and natural bronchopneumonias caused by Actinobacillus pleuropneumoniae or Staphylococcus aureus, and from embolic and diffuse interstitial pneumonia, caused by Staph. aureus or Arcanobacterium pyogenes and Streptococcus suis serotype 2, respectively. By comparing normal and diseased lung tissue from the same lungs, increased diffuse pSP-D immunoreactivity was seen in the surfactant in both acute and chronic bronchopneumonias, while such increased expression of pSP-D was generally not present in the interstitial pneumonias. Co-localization of pSP-D, alveolar macrophages and bacteria was demonstrated, and pSP-D showed a patchy distribution on the membranes of alveolar macrophages. SP-D immunoreactivity was intracellular in dendritic cells. The dendritic cells were identified by their morphology, the absence of macrophage marker immunoreactivity and the presence of dendritic cell marker immunoreactivity. Increased expression of pSP-D in the surfactant coincided with presence of pSP-D-positive dendritic cells in bronchus-associated lymphoid tissue (BALT), indicating a possible transport of pSP-D through the specialized M cells overlying (BALT). In conclusion, we have shown that pSP-D expression in the lung surfactant is induced by bacterial infection by an aerogenous route rather than by a haematogenous route, and that the protein interacts specifically with alveolar macrophages and with dendritic cells in microbial-induced BALT. The function of the interaction between pSP-D and dendritic cells in BALT remain unclear, but pSP-D could represent a link between the innate and adaptive immune system, facilitating the bacterial antigen presentation by dendritic cells in BALT.

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“…The observation that Survanta increased lung cell apoptosis is intriguing because lung surfactant has been reported to promote phagocytic clearance of pathogens, unwanted cells and particles. [21][22][23]35 One possible explanation for this discrepancy is that the amount of Survanta used in the present study may exceed the capacity limit of phagocytic cell clearance. Thus, only a high-dose of Survanta was able to produce apoptosis in vivo.…”

Section: Discussionmentioning

confidence: 71%

“…[21][22][23] To test whether pulmonary surfactant can promote the clearance of apoptotic cells in vivo, we treated rats intratracheally with apoptotic macrophages in the absence or presence of various doses of Survanta. The effect of Survanta administration on lung cell apoptosis was determined by TUNEL.…”

Section: Effect Of Exogenous Surfactant On Lung Cell Apoptosis In Vivomentioning

confidence: 99%

“…Certain components of lung surfactant, such as surfactant protein-A (SP-A) and SP-D, have been reported to facilitate phagocytic clearance of dying cells and pathogens by macrophages. [20][21][22][23] Increased macrophage clearance of dying or apoptotic cells would therefore reduce the number of apoptotic cells in the lung. On the other hand, excessive accumulation of lung surfactant may impair or overwhelm the phagocytic clearance function of macrophages, thus increasing the number of pulmonary apoptotic cells.…”

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confidence: 99%

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Role of lung surfactant in phagocytic clearance of apoptotic cells by macrophages in rats

Wang

Scabilloni

Antonini

et al. 2006

Laboratory Investigation

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Two of the common features of inflammatory lung diseases are the increased production of pulmonary surfactant and the induction of lung cell apoptosis. However, the relationship between these two events has not been addressed. To investigate the role of surfactant in pulmonary inflammation and apoptosis, we instilled natural lung surfactant (Survanta) (1.6-12.5 mg) into the rat lungs and determined the number of alveolar macrophages (AMs) and apoptotic lung cells. High-dose treatments of Survanta (46.25 mg/rat) caused an increase in macrophage cell influx and lung cell apoptosis at 4 weeks post-treatment. In vitro studies using lavaged macrophages showed Survanta did not cause apoptosis. We then examined the role of Survanta on ability of macrophages phagocytizing apoptotic cells. This study demonstrated that macrophages were able to eliminate apoptotic cells more efficiently in the absence of surfactant than in its presence. Keywords: Survanta; rat lung; apoptosis; clearance; alveolar macrophage Lung surfactant is synthesized by alveolar epithelial type II cells and is composed of approximately 80% phospholipids, 10% proteins and 10% neutral lipids. Pulmonary surfactant exists in two major compartments in the lung: the intracellular or storage compartment in the cytoplasm of alveolar type II cells and the extracellular compartment in the alveoli and distal airways. Under normal circumstances, these two pools of surfactant are maintained relatively constant. Alveolar macrophages (AMs) and type II cells are responsible for degradation of the surfactant 1,2 and exhibit increased lipid uptake and degradation in inflamed animal lungs. 3 Many toxicants, both chemical and particulate, appear to interfere with this balance. 4

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Surfactant Protein D Reduces Alveolar Macrophage Apoptosis In Vivo

Cited by 144 publications

References 34 publications

Mannose‐binding lectin engagement with late apoptotic and necrotic cells

Mannose‐binding lectin engagement with late apoptotic and necrotic cells

Pulmonary infections in swine induce altered porcine surfactant protein D expression and localization to dendritic cells in bronchial‐associated lymphoid tissue

Role of lung surfactant in phagocytic clearance of apoptotic cells by macrophages in rats

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