ArticleAmerican journal of respiratory and critical care medicine2008
Surfactant proteins A and D suppress alveolar macrophage phagocytosis via interaction with SIRP alpha.
Article in American journal of respiratory and critical care medicine, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 129 papers.
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Who cites it
129 citing papers in PubMed, 199 citations in OpenAlex.
- Serine protease inhibitor A3 is a soluble SIRPα ligand that suppresses inflammation and antitumor immunity.Nature immunology · 2026Article
- Biophysical rationale and emerging clinical perspectives of surfactants in thoracic surgery: a translational review.Langenbeck's archives of surgery · 2026Review
- Biosurfactant-Based Interventions for Improving Lung Function and Controlling Inflammation.Pharmaceutical research · 2026Review
- The cell with many faces: lung macrophage plasticity and function in response to environmental and pathogenic insults.Physiological reviews · 2026Review
- Progress in immunological research on innate effectors in xenotransplantation.Surgery today · 2026Review
- Macrophages orchestrate antiviral defense and epithelial repair in a human iPSC-derived alveolar air-liquid interface.JCI insight · 2026Article
- Recent perspectives on macrophage memory: types, mechanisms, and characteristics in pulmonary diseases.Cell communication and signaling : CCS · 2026Review
- Review
- Immune checkpoint molecules signal regulatory protein alpha in the development of hepatocellular carcinoma.World journal of gastrointestinal oncology · 2025Review
- Heterogeneity of Lung Phagocytes and Clearance of Apoptotic Cells in Lung Injury and Repair.Seminars in respiratory and critical care medicine · 2025Review
- Geranylgeranyl diphosphate synthase deficiency impairs efferocytosis and resolution of acute lung injury.Respiratory research · 2025Article
- Alveolar Macrophages in Viral Respiratory Infections: Sentinels and Saboteurs of Lung Defense.International journal of molecular sciences · 2025Review
- The Immune Modulatory Role of Surfactants inJournal of inflammation research · 2025Review
- Lung Immune Cell Niches and the Discovery of New Cell Subtypes.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Review
- The role of alveolar macrophages in viral respiratory infections and their therapeutic implications.Biochemistry and biophysics reports · 2024Review
- SIRPα modulates the podocyte cytoskeleton through influencing the phosphorylation of FAK at tyrosine residue 597.Acta biochimica et biophysica Sinica · 2024Article
- Surfactant protein D prevents mucin overproduction in airway goblet cells via SIRPα.Scientific reports · 2024Article
- Neuroimmune pathways involvement in neurodegeneration of R6/2 mouse model of Huntington's disease.Frontiers in cellular neuroscience · 2024Article
- Efferocytosis and Respiratory Disease.International journal of molecular sciences · 2023Review
- Alveolar macrophages in tissue homeostasis, inflammation, and infection: evolving concepts of therapeutic targeting.The Journal of clinical investigation · 2023Review
69 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
rationaleEfficient removal of apoptotic cells is essential for the resolution of acute pulmonary inflammation. Alveolar macrophages ingest apoptotic cells less avidly than other professional phagocytes at rest but overcome this defect during acute inflammation. Surfactant protein (SP)-A and SP-D are potent modulators of macrophage function and may suppress clearance of apoptotic cells through activation of the transmembrane receptor signal inhibitory regulatory protein alpha (SIRP alpha).
objectivesTo investigate whether binding of SP-A and SP-D to SIRP alpha on alveolar macrophages suppresses apoptotic cell clearance.
methodsPhagocytosis of apoptotic cells was assessed using macrophages pretreated with SP-A, SP-D, or the collectin-like molecule C1q. Binding of SP-A and SP-D to SIRP alpha was confirmed in vitro using blocking antibodies and fibroblasts transfected with active and mutant SIRP alpha. The effects of downstream molecules SHP-1 and RhoA on phagocytosis were studied using SHP-1-deficient mice, sodium stibogluconate, and a Rho kinase inhibitor. Lipopolysaccharide was given to chimeric mice to study the effects of SP-A and SP-D binding on inflammatory macrophages. MEASUREMENTS AND MAIN
resultsPreincubation of macrophages with SP-A or SP-D suppressed apoptotic cell clearance. Surfactant suppression of macrophage phagocytosis was reversed by blocking SIRP alpha and inhibiting downstream molecules SHP-1 and RhoA. Macrophages from inflamed lungs ingested apoptotic cells more efficiently than resting alveolar macrophages. Recruited mononuclear phagocytes with low levels of SP-A and SP-D mediated this effect.
conclusionsSP-A and SP-D tonically inhibit alveolar macrophage phagocytosis by binding SIRP alpha. During acute pulmonary inflammation, defects in apoptotic cell clearance are overcome by recruited mononuclear phagocytes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.