Abstract
Surfactant proteins A and D (SP-A and SP-D) are lung collectins composed of two regions, a globular head domain that binds PAMPs and a collagenous tail domain that initiates phagocytosis. We provide evidence that SP-A and SP-D act in a dual manner, to enhance or suppress inflammatory mediator production depending on binding orientation. SP-A and SP-D bind SIRPalpha through their globular heads to initiate a signaling pathway that blocks proinflammatory mediator production. In contrast, their collagenous tails stimulate proinflammatory mediator production through binding to calreticulin/CD91. Together a model is implied in which SP-A and SP-D help maintain a non/anti-inflammatory lung environment by stimulating SIRPalpha on resident cells through their globular heads. However, interaction of these heads with PAMPs on foreign organisms or damaged cells and presentation of the collagenous tails in an aggregated state to calreticulin/CD91, stimulates phagocytosis and proinflammatory responses.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Antigens, Differentiation*
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Calreticulin / immunology
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Calreticulin / metabolism*
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Cells, Cultured
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Collectins / chemistry
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Collectins / immunology
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Collectins / metabolism*
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Complement C1q / metabolism
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Cytokines / metabolism
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Enzyme Activation
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Humans
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Inflammation / metabolism*
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Intracellular Signaling Peptides and Proteins
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Lung / cytology
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Lung / metabolism*
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Macrophages, Alveolar / cytology
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Macrophages, Alveolar / metabolism
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Membrane Glycoproteins / immunology
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Membrane Glycoproteins / metabolism*
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Mice
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Mitogen-Activated Protein Kinases / metabolism
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Neural Cell Adhesion Molecule L1 / immunology
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Neural Cell Adhesion Molecule L1 / metabolism*
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Protein Binding
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Protein Tyrosine Phosphatase, Non-Receptor Type 6
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Protein Tyrosine Phosphatases / metabolism
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Pulmonary Surfactant-Associated Protein A / chemistry
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Pulmonary Surfactant-Associated Protein A / immunology
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Pulmonary Surfactant-Associated Protein A / metabolism
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Pulmonary Surfactant-Associated Protein D / chemistry
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Pulmonary Surfactant-Associated Protein D / immunology
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Pulmonary Surfactant-Associated Protein D / metabolism
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Receptors, Immunologic*
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p38 Mitogen-Activated Protein Kinases
Substances
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Antigens, Differentiation
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Calreticulin
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Collectins
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Cytokines
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Intracellular Signaling Peptides and Proteins
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Membrane Glycoproteins
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Neural Cell Adhesion Molecule L1
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Pulmonary Surfactant-Associated Protein A
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Pulmonary Surfactant-Associated Protein D
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Receptors, Immunologic
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Complement C1q
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Mitogen-Activated Protein Kinases
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p38 Mitogen-Activated Protein Kinases
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PTPN6 protein, human
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Protein Tyrosine Phosphatase, Non-Receptor Type 6
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Protein Tyrosine Phosphatases
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Ptpn6 protein, mouse