Surfactant Proteins A and D Enhance Pulmonary Clearance of<i>Pseudomonas aeruginosa</i>

Giannoni, Éric; Sawa, Teiji; Allen, Lennell; Wiener-Kronish, Jeanine P.; Hawgood, Sam

doi:10.1165/rcmb.2005-0461oc

Cited by 97 publications

(95 citation statements)

References 43 publications

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“…SP-D is also known to recognize various microbial pathogens by binding to the carbohydrate moieties on bacterial surfaces, including that of P. aeruginosa, and enhances phagocytic clearance of these microbes by macrophages and neutrophils (25,(52)(53)(54)(55). SP-D is known to bind various strains of P. aeruginosa but can only agglutinate certain strains of this pathogen (30,56).…”

Section: Discussionmentioning

confidence: 99%

Innate Immune Collectin Surfactant Protein D Simultaneously Binds Both Neutrophil Extracellular Traps and Carbohydrate Ligands and Promotes Bacterial Trapping

Douda

Jackson

Grasemann

et al. 2011

The Journal of Immunology

112

100

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Neutrophils release DNA-based extracellular traps to capture and kill bacteria. The mechanism(s) and proteins that promote neutrophil extracellular trap (NET)-mediated bacterial trapping are not clearly established. Surfactant protein D (SP-D) is an innate immune collectin present in many mucosal surfaces. We hypothesized that SP-D can bind both the pathogens and NETs to augment NET-mediated bacterial trapping. To test this hypothesis, we used LPS and Pseudomonas aeruginosa pneumonia mouse models and performed in vivo and ex vivo assays. In this study, we show that NETs are produced by the neutrophils recruited to the airways in response to the bacterial ligand. Notably, NETs are detected as short fragments of DNA–protein complexes in the airways as opposed to the long stringlike structures seen in ex vivo cultures. SP-D recognizes both the short NET fragments and the long NET DNA structures. SP-D–NET copurification studies further show that SP-D can simultaneously recognize NETs and carbohydrate ligands in vivo. Similar to the LPS model, soluble DNA–protein complexes and increased amounts of SP-D are detected in the murine model of P. aeruginosa pneumonia. We then tested the effect of SP-D on NET-mediated trapping of P. aeruginosa by means of Western blots, fluorescence microscopy, and scanning electron microscopy. Results of these experiments show that SP-D microagglutinates P. aeruginosa and allows an efficient bacterial trapping by NETs. Collectively, these findings provide a unique biological relevance for SP-D–DNA interactions and places SP-D as an important innate immune protein that promotes bacterial trapping by NETs during neutrophil-mediated host defense.

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Section: Discussionmentioning

confidence: 99%

Innate Immune Collectin Surfactant Protein D Simultaneously Binds Both Neutrophil Extracellular Traps and Carbohydrate Ligands and Promotes Bacterial Trapping

Douda

Jackson

Grasemann

et al. 2011

The Journal of Immunology

112

100

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“…In addition, the levels of lung collectins often increase following microbial challenge (76). Mice lacking the SP-A gene show increased bacterial proliferation, more-intense lung inflammation, and increased dissemination following challenge with a variety of bacteria (21,28,39,(49)(50)(51). SP-D-deficient mice exhibit a more complex phenotype (4,40).…”

Section: Mrmentioning

confidence: 99%

“…SP-D-deficient mice exhibit a more complex phenotype (4,40). However, they also show a decreased uptake of bacteria by macrophages and an altered inflammatory response to bacterial challenge (21,51). Although SP-A and SP-D are synthesized by type II and bronchiolar epithelial cells, SP-D is found in many other tissues, including salivary glands, where it could interact with potential pulmonary pathogens that initially colonize the upper respiratory tract (55).…”

Section: Mrmentioning

confidence: 99%

Recognition of Bacterial Surface Polysaccharides by Lectins of the Innate Immune System and Its Contribution to Defense against Infection: the Case of Pulmonary Pathogens

et al. 2008

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5Many pathogenic bacterial species are classified into serological types, distinguished by their carbohydrate-rich surface antigens. These antigens are referred to as serotypic epitopes or glycoepitopes. Glycoepitopes are most commonly associated with capsular polysaccharides (CPS) or the O-antigen domains of bacterial lipopolysaccharides (LPS).The association of specific bacterial serotypes of a given genus with defined clinical infections is a common phenomenon that applies to a variety of gram-negative bacteria and gram-positive bacteria. As discussed below, of the 77 distinct capsular serotypes in the species Klebsiella pneumoniae, only 25 account for most pulmonary and blood infections (12). Likewise, of the more than 90 capsular serotypes of Streptococcus pneumoniae, only 23 account for most infections, and these are included in the current capsular vaccine (25).The surfaces of the pulmonary pathogens Klebsiella pneumoniae and Streptococcus pneumoniae are coated with a variety of glycoconjugates that confer specific properties. For example, the polysaccharide capsules enable these pathogens to resist phagocytosis. In a few cases, it has been argued that serotype-associated differences in capsular size contribute to virulence and the high frequency of isolation. However, there is no satisfactory explanation why only a limited number of capsular serotypes are responsible for most infections (12,25).Because lectins are important components of the lung's innate immune system, it is reasonable to hypothesize that differences in the frequencies of isolation of specific serotypes in the setting of pneumonia are in part determined by the recognition, or the lack of recognition, of their corresponding glycoepitopes by lectins. We propose that the lack of recognition of glycoconjugates by one or more lectins of the lung contributes to the high frequency of isolation from pneumonia patients of the pulmonary pathogens bearing reactive glycoepitopes. Conversely, lectins that recognize serotype-specific glycoepitopes contribute to the eradication of these serotypes, resulting in a lower frequency of their isolation from clinical samples.In this review, we first correlate the sugar specificities of several types of lung lectins with the glycoconjugates on the surfaces of selected pulmonary pathogens. We then briefly describe in vitro data that suggest mechanisms through which the lung C-type lectins contribute to the elimination of specific glycoepitope-bearing serotypes. Finally, we review available evidence supporting our hypothesis that the high frequency of isolation of serotypes bearing a specific glycoepitope results from the ability of these serotypes to evade recognition by lectins of the innate immune system. PULMONARY LECTINS OF THE INNATE IMMUNE SYSTEMDuring the last 3 decades, there has been intensive research on animal lectins (59, 90). Although lung lectins play a variety of homeostatic roles (38, 89), considerable research has focused on the contributions of several lectins to the innate, natural defense s...

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“…By binding to a wide variety of pathogens, SP-A opsonizes and enhances pathogen uptake by phagocytes. In vivo studies using SP-A-deficient (SP-A 2/2 ) mice have shown that SP-A regulates responses involved in both initiation and potentiation of inflammation by decreasing production of proinflammatory cytokines, such as tumor necrosis factor-a (TNF-a), in response to lipopolysaccharide (4) or by accelerating the clearance of a variety of pathogens (5)(6)(7)(8)(9). Thus, SP-A contributes to multiple aspects of pulmonary host defense.…”

mentioning

confidence: 99%

The Role of Surfactant Protein A in Bleomycin-induced Acute Lung Injury

Goto¹,

Ledford²,

Mukherjee³

et al. 2010

Am J Respir Crit Care Med

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Rationale: Surfactant protein A (SP-A) is a collectin family member that has multiple immunomodulatory roles in lung host defense. SP-A levels are altered in the bronchoalveolar lavage (BAL) fluid and serum of patients with acute lung injury and acute respiratory distress syndrome, suggesting the importance of SP-A in the pathogenesis of acute lung injury. Objectives: Investigate the role of SP-A in the murine model of noninfectious lung injury induced by bleomycin treatment. Methods: Wild-type (WT) or SP-A deficient (SP-A 2/2 ) mice were challenged with bleomycin, and various indices of lung injury were analyzed. Measurements and Main Results: On challenge with bleomycin, SP-A 2/2 mice had a decreased survival rate as compared with WT mice. SP-A 2/2 mice had a higher degree of neutrophil-dominant cell recruitment and the expression of the inflammatory cytokines in BAL fluid than did WT mice. In addition, SP-A 2/2 mice had increased lung edema as assessed by the increased levels of intravenously injected Evans blue dye leaking into the lungs. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling and active caspase-3 staining suggested the increased apoptosis in the lung sections from SP-A 2/2 mice challenged with bleomycin. SP-A also specifically reduced bleomycin-induced apoptosis in mouse lung epithelial 12 cells in vitro. Moreover, intratracheal administration of exogenous SP-A rescued the phenotype of SP-A 2/2 mice in vivo. Conclusions: These data suggest that SP-A plays important roles in modulating inflammation, apoptosis, and epithelial integrity in the lung in response to acute noninfectious challenges.

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Surfactant Proteins A and D Enhance Pulmonary Clearance ofPseudomonas aeruginosa

Cited by 97 publications

References 43 publications

Innate Immune Collectin Surfactant Protein D Simultaneously Binds Both Neutrophil Extracellular Traps and Carbohydrate Ligands and Promotes Bacterial Trapping

Innate Immune Collectin Surfactant Protein D Simultaneously Binds Both Neutrophil Extracellular Traps and Carbohydrate Ligands and Promotes Bacterial Trapping

Recognition of Bacterial Surface Polysaccharides by Lectins of the Innate Immune System and Its Contribution to Defense against Infection: the Case of Pulmonary Pathogens

The Role of Surfactant Protein A in Bleomycin-induced Acute Lung Injury

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