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Surfactant protein D reduces alveolar macrophage apoptosis in vivo
Howard Clark1, Nades Palaniyar, Peter Strong
1Medical Research Council Immunochemistry Unit, Department of Biochemistry, University of Oxford, Oxford, United Kingdom. howard.clark@bioch.ox.ac.uk
Abstract:
Surfactant protein D (SP-D) is a molecule of the innate immune system that recognizes the patterns of surface carbohydrate on pathogens and targets them for phagocytosis and killing. SP-D-deficient mice show an increased number of macrophages in the alveolar space, excess surfactant phospholipid, overproduction of reactive oxygen species, and the development of emphysema. We report here that SP-D-deficient mice have a 5- to 10-fold increase in the number of apoptotic and necrotic alveolar macrophages, as defined by annexin V and propidium iodine staining, respectively. Intrapulmonary administration of a truncated 60-kDa fragment of human recombinant SP-D reduces the number of apoptotic and necrotic alveolar macrophages and partially corrects the lipid accumulation in SP-D-deficient mice. The same SP-D fragment binds preferentially to apoptotic and necrotic alveolar macrophages in vitro, suggesting that SP-D contributes to immune homeostasis in the lung by recognizing and promoting removal of necrotic and apoptotic cells.
Insights
Surfactant protein D (SP-D) deficiency increases lung cell death. Administering an SP-D fragment reduces this cell death and corrects lipid buildup, suggesting SP-D’s role in lung immune homeostasis.
Area of Science:
- Pulmonary immunology
- Innate immunity
- Cellular biology
Background:
- Surfactant protein D (SP-D) is an innate immune molecule recognizing pathogen carbohydrates.
- SP-D deficiency in mice leads to alveolar macrophages accumulation, excess surfactant phospholipid, reactive oxygen species, and emphysema.
Purpose of the Study:
- To investigate the role of SP-D in the clearance of apoptotic and necrotic alveolar macrophages.
- To evaluate the therapeutic potential of an SP-D fragment in SP-D-deficient mice.
Main Methods:
- SP-D-deficient mice were analyzed for apoptotic and necrotic alveolar macrophages using annexin V and propidium iodine staining.
- A truncated 60-kDa fragment of human recombinant SP-D was administered intrapulmonary.
- In vitro binding assays were performed using the SP-D fragment and alveolar macrophages.
Main Results:
- SP-D-deficient mice exhibited a 5- to 10-fold increase in apoptotic and necrotic alveolar macrophages.
- Intrapulmonary administration of the SP-D fragment reduced these cells and partially corrected lipid accumulation.
- The SP-D fragment preferentially bound to apoptotic and necrotic alveolar macrophages in vitro.
Conclusions:
- SP-D plays a crucial role in maintaining lung immune homeostasis by clearing apoptotic and necrotic cells.
- SP-D fragment administration shows therapeutic potential for SP-D-related lung pathologies.