Host Defense Functions of Pulmonary Surfactant

Wright, Jo Rae

doi:10.1159/000078172

Cited by 84 publications

(59 citation statements)

References 71 publications

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“…The alveolar epithelium of the lungs is a combination of type I cells that build the air-blood barrier and type II cells that synthesize and secrete surfactant. The lung surfactant proteins A and D are part of the pulmonary innate immune system (Wu et al, 2003;Wright, 2004;Jung et al, 2005) and influence inflammatory processes (Chabot et al, 2003;Gardai et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Microscopic Anatomy of the Lower Respiratory System of the African Giant Pouched Rat (Cricetomys gambianus, Waterhouse 1840)

et al. 2011

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Section: Introductionmentioning

confidence: 99%

Microscopic Anatomy of the Lower Respiratory System of the African Giant Pouched Rat (Cricetomys gambianus, Waterhouse 1840)

et al. 2011

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“…tein homolog SP-D, SP-A plays an important role in pulmonary innate immunity by recognizing canonical patterns on microbial surfaces (1)(2)(3)(4)(5)(6)(7)(8). These host defense proteins protect the lung from infection by recognizing the carbohydrate and/or lipid component on pathogens, including bacteria, virus, and fungi, and by helping to initiate various clearance mechanisms (9).…”

mentioning

confidence: 99%

Crystallographic Complexes of Surfactant Protein A and Carbohydrates Reveal Ligand-induced Conformational Change

Shang

Rynkiewicz

McCormack

et al. 2011

Journal of Biological Chemistry

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Surfactant protein A (SP-A Surfactant protein A (SP-A)2 is an abundant protein associated with pulmonary surfactant. Together with the lung protein homolog SP-D, SP-A plays an important role in pulmonary innate immunity by recognizing canonical patterns on microbial surfaces (1-8). These host defense proteins protect the lung from infection by recognizing the carbohydrate and/or lipid component on pathogens, including bacteria, virus, and fungi, and by helping to initiate various clearance mechanisms (9).SP-A and SP-D are members of the collectin family, a subgroup of C-type (calcium-dependent) lectins (10), which also includes serum proteins, such as human mannose-binding protein (MBP) or lectin and bovine conglutinin (11). SP-A and SP-D have distinct preferences among the mannose-type saccharides and other glycans, which may enable these proteins to interact differentially with respiratory pathogens (12). Where the two collectins share a common microbial target, such as LPS from the outer membrane of Gram-negative bacteria, the microbial features recognized may be dissimilar. For instance, SP-D interacts with the LPS core saccharides, whereas SP-A prefers the lipid A domain (13,14). Distinct mechanisms, which may not require lectin interactions, may underlie such divergent interactions. For example, SP-D binds to influenza A virus through lectin-type interactions (15, 16), whereas influenza A virus binds to SP-A via interactions involving the sialylated N-linked carbohydrate attached to the C-terminal domain of SP-A (17, 18). SP-A, the more abundant of the two lung collectins, thus plays an important and complementary role in pathogen clearance by interacting with microbial patterns that are not well recognized by SP-D and vice versa.The carbohydrate recognition domain (CRD) confers the calcium-dependent lectin activity and is responsible primarily for pathogen recognition. Structural and other types of studies show that the CRD of C-type lectins characteristically folds into a canonical double-loop structure. The two loops, the long loop (residues 181-204) and the short loop (residues 171-177), are stabilized by disulfide bonds at the ends of the loops and bound calcium ions. These lectins recognize their carbohydrate ligands through extensive interactions between two pyranose hydroxyl groups of the sugar, the calcium ion, and four to five residues of the lectin site (10). Fragments corresponding to the CRD or the neck and CRD (NCRD) of these large multidomain proteins have provided useful tools for studies of collectin-ligand recognition and binding interactions. * This work was supported, in whole or in part, by National Institutes of Health Grant AI083222 from NIAID (to B. A. S.). This work was also supported by a Department of Veterans Affairs merit award (to F. X. M.). The atomic coordinates and structure factors (codes 3PAK, 3PAQ, 3PAR, and 3PBF)

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“…The surfactant proteins A (SP-A) and D (SP-D) are members of the collectin protein family, and they have comparable potential to interact with cells and microorganisms (Crouch and Wright, 2001;Hawgood and Poulain, 2001). The lung collectins, SP-A and SP-D, are part of the pulmonary innate immune system (Crouch and Wright, 2001;McCormack and Whitsett, 2002;Wu et al, 2003;Wright, 2004) and influence inflammatory processes (Chabot et al, 2003;Gardai et al, 2003). Within the alveolar lumen, SP-A is associated with tubular myelin, whereas SP-D exists mainly free in the hypophase (Wright, 1997;McCormack and Whitsett, 2002).…”

mentioning

confidence: 99%

Design‐based stereological analysis of the lung parenchymal architecture and alveolar type II cells in surfactant protein A and D double deficient mice

et al. 2005

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Alveolar epithelial type II cells synthesize and secrete surfactant. The surfactant-associated proteins A and D (SP-A and SP-D), members of the collectin protein family, participate in pulmonary immune defense, modulation of inflammation, and surfactant metabolism. Both proteins are known to have overlapping as well as distinct functions. The present study provides a design-based stereological analysis of adult mice deficient in both SP-A and SP-D (A Ϫ D Ϫ ) with special emphasis on parameters characterizing alveolar architecture and surfactant-producing type II cells. Compared to wild-type, A Ϫ D Ϫ mice have fewer and larger alveoli, an increase in the number and size of type II cells, as well as more numerous and larger alveolar macrophages. More surfactant-storing lamellar bodies are seen in type II cells, leading to a threefold increase in the total volume of lamellar bodies per lung, but the mean volume of a single lamellar body remains constant. These results demonstrate that chronic deficiency of SP-A and SP-D in mice leads to parenchymal remodeling, type II cell hyperplasia and hypertrophy, and disturbed intracellular surfactant metabolism. The design-based stereological approach presented here provides a framework for the quantitative lung structure analysis in gene-manipulated mice as well as in human lung disease.

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Host Defense Functions of Pulmonary Surfactant

Cited by 84 publications

References 71 publications

Microscopic Anatomy of the Lower Respiratory System of the African Giant Pouched Rat (Cricetomys gambianus, Waterhouse 1840)

Microscopic Anatomy of the Lower Respiratory System of the African Giant Pouched Rat (Cricetomys gambianus, Waterhouse 1840)

Crystallographic Complexes of Surfactant Protein A and Carbohydrates Reveal Ligand-induced Conformational Change

Design‐based stereological analysis of the lung parenchymal architecture and alveolar type II cells in surfactant protein A and D double deficient mice

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