Surfactant protein D and asthma (original) (raw)
American Journal of Respiratory and Critical Care Medicine, 2011
Rationale: Surfactant protein D (SP-D), a 43-kD collectin, is synthesized and secreted by airway epithelia as a dodecamer formed by assembly of four trimeric subunits. We have previously shown that the quaternary structure of SP-D can be altered during inflammatory lung injury through its modification by S-nitrosylation, which in turn alters its functional behavior producing a proinflammatory response in effector cells. Objectives: We hypothesized that alterations in structure and function of SP-D may occur in humans with acute allergic inflammation. Methods: Bronchoalveolar lavage (BAL) fluid was collected from 15 nonsmoking patients with mild intermittent allergic asthma before and 24 hours after segmental provocation with saline, allergen, LPS, and mixtures of allergen and LPS. Structural modifications of SP-D were analyzed by native and sodium dodecyl sulfate gel electrophoresis. Measurements and Main Results: The multimeric structure of native SP-D was found to be disrupted after provocation with allergen or a mixture of allergen and LPS. Interestingly, under reducing conditions, sodium dodecyl sulfate-polyacrylamide gel electrophoresis demonstrated that 7 of 15 patients with asthma developed an abnormal cross-linked SP-D band after segmental challenge with either allergen or a mixture of allergen with LPS but not LPS alone. Importantly, patients with asthma with cross-linked SP-D demonstrated significantly higher levels of BAL eosinophils, nitrogen oxides, IL-4, IL-5, IL-13, and S-nitrosothiol-SP-D compared with patients without cross-linked SP-D. Conclusions: We conclude that segmental allergen challenge results in changes of SP-D multimeric structure and that these modifications are associated with an altered local inflammatory response in the distal airways.
Bronchial Asthma and Salivary Surfactant Protein D: Review Article
The Egyptian Journal of Hospital Medicine, 2021
Background: Chronic bronchial inflammation underlies asthma, which is a complex disease with varied and largely reversible blockage of the respiratory route. Asthma is a major public health issue that affects people of all ages around the world. Many countries are seeing an increase in the prevalence of this disease, particularly among children. Among children, asthma is the most frequent long-term condition, accounting for more than half of all missed school days, emergency room consultations, and hospitalizations. Surfactant Protein D, a pattern-recognition molecule, dampens elevated levels of particular antibodies, alveolar macrophage accumulation, eosinophilia, and subepithelial fibrosis and mucous metaplasia, as well as airway hyper-reactivity in allergic asthma in vivo. Objective: In order to discover the connection between children's bronchial asthma and surfactant protein D. Conclusion: Salivary SP-D is a simple, low-cost, quick, and noninvasive way to collect saliva from children. Salivary SP-D levels may be linked to asthma exacerbation severity and peripheral airway resistance.
The Journal of Allergy and Clinical Immunology, 2008
The acute inflammatory airway response is characterized by a time-dependent onset followed by active resolution. Emerging evidence suggests that epithelial cells of the proximal and distal air spaces release host defense mediators that can facilitate both the initiation and the resolution part of inflammatory airway changes. These molecules, also known as the hydrophilic surfactant proteins (surfactant protein [SP]-A and SP-D) belong to the class of collagenous lectins (collectins). The collectins are a small family of soluble pattern recognition receptors containing collagenous regions and C-type lectin domains. SP-A and SP-D are most abundant in the lung. Because of their structural uniqueness, specific localization, and functional versatility, lung collectins are important players of the pulmonary immune responses. Recent studies in our laboratory and others indicated significant associations of lung collectin levels with acute and chronic airway inflammation in both animal models and patients, suggesting the usefulness of these molecules as disease biomarkers. Research on wild-type and mutant recombinant molecules in vivo and in vitro showed that SP-A and SP-D bind carbohydrates, lipids, and nucleic acids with a broad-spectrum specificity and initiate phagocytosis of inhaled pathogens as well as apoptotic cells. Investigations on gene-deficient and conditional overexpresser mice indicated that lung collectins also directly modulate innate immune cell function and T-cell-dependent inflammatory events. Thus, these molecules have a unique, dual-function capacity to induce pathogen elimination and control proinflammatory mechanisms, suggesting a potential suitability for therapeutic prevention and treatment of chronic airway inflammation. This article reviews evidence supporting that the lung collectins play an immune-protective role and are essential for maintenance of the immunologic homeostasis in the lung.
Journal of Biological Chemistry, 2002
The N-terminal domains of the lung collectins, surfactant proteins A (SP-A) and D (SP-D), are critical for surfactant phospholipid interactions and surfactant homeostasis, respectively. To further assess the importance of lung collectin N-terminal domains in surfactant structure and function, a chimeric SP-D/SP-A (D/A) gene was constructed by substituting nucleotides encoding amino acids Asn 1 -Ala 7 of rat SP-A with the corresponding N-terminal sequences from rat SP-D, Ala 1 -Asn 25 .
Respiratory Research, 2012
Background: Allergen-containing subpollen particles (SPP) are released from whole plant pollen upon contact with water or even high humidity. Because of their size SPP can preferentially reach the lower airways where they come into contact with surfactant protein (SP)-D. The aim of the present study was to investigate the influence of SP-D in a complex three-dimensional human epithelial airway model, which simulates the most important barrier functions of the epithelial airway. The uptake of SPP as well as the secretion of pro-inflammatory cytokines was investigated. Methods: SPP were isolated from timothy grass and subsequently fluorescently labeled. A human epithelial airway model was built by using human Type II-pneumocyte like cells (A549 cells), human monocyte derived macrophages as well as human monocyte derived dendritic cells. The epithelial cell model was incubated with SPP in the presence and absence of surfactant protein D. Particle uptake was evaluated by confocal microscopy and advanced computer-controlled analysis. Finally, human primary CD4 + T-Cells were added to the epithelial airway model and soluble mediators were measured by enzyme linked immunosorbent assay or bead array. Results: SPP were taken up by epithelial cells, macrophages, and dendritic cells. This uptake coincided with secretion of pro-inflammatory cytokines and chemokines. SP-D modulated the uptake of SPP in a cell type specific way (e.g. increased number of macrophages and epithelial cells, which participated in allergen particle uptake) and led to a decreased secretion of pro-inflammatory cytokines. Conclusion: These results display a possible mechanism of how SP-D can modulate the inflammatory response to inhaled allergen.
Surfactant proteins SP-A and SP-D in human health and disease
Archivum immunologiae et therapiae experimentalis
Surfactant proteins A (SP-A) and D (SP-D) are lung surfactant-associated hydrophilic proteins that have been implicated in surfactant homeostasis and pulmonary innate immunity. They are collagen-containing C-type (calcium-dependent) lectins, called collectins, and are structurally similar to mannose-binding protein of the lectin pathway of the complement system. Being carbohydrate pattern-recognition molecules, they recognize a broad spectrum of pathogens and allergens via the lectin domain, with subsequent activation of immune cells via the collagen region, thus offering protection against infection and allergenic challenge. SP-A and SP-D have been shown to be involved in viral neutralization, clearance of bacteria, fungi, and apoptotic and necrotic cells, down-regulation of allergic reaction, and resolution of inflammation. Studies on single-nucleotide polymorphism, protein levels in broncho-alveolar lavage, and gene knock-out mice have clearly indicated an association between SP-...
Clinical & Experimental Allergy, 2001
Background Increasing evidence suggests that pulmonary surfactant protein A (SP-A) and D (SP-D) participate in the lung defence against pathogens. However, the role of surfactant proteins in the pathogenesis of allergen-induced airway inflammation has not been elucidated. In this study we examined the levels and distributions of SPA and SP-D in a dust mite (Dermatophagoides pteronyssinus, Der p) allergen-induced murine model of asthma. Methods The concentration of SPA and SP-D in the bronchoalveolar lavage fluid (BALF) and the distribution of surfactant proteins in the lung were assayed by ELISA and immunohistochemistry methods, respectively. The effect of surfactant proteins on allergen-induced pulmonary lymphocyte proliferation was also studied. Results We demonstrated that there were marked reductions of SPA and SP-D levels in the BALF of Der p-sensitized BALB/c mice at 48±72 h after allergen challenge (AC). Both purified SPA and SP-D were able to suppress, in a dose dependent manner, Der pstimulated intrapulmonary lymphocyte proliferation of naõ Ève mice with saline or allergen challenge, or of Der p-sensitized mice with saline challenge. On the contrary, this suppressive effect was mild (, 9%) on lymphocytes from sensitized mice after AC. Conclusion These results indicated the involvement of pulmonary surfactant proteins in the allergic bronchial inflammation of sensitized mice.
Surfactant protein D binding to alveolar macrophages
Biochemical Journal, 1994
Surfactant protein D (SP-D) is a lung-specific protein, synthesized and secreted by lung epithelial cells. It belongs to group III of the family of C-type lectins; each member of this group has an unusual overall structure consisting of multiple globular ‘head’ regions (which contain the C-type lectin domains) linked by triple-helical, collagen-like, strands. This group includes the surfactant protein A (SP-A) and the serum proteins mannan-binding protein, conglutinin and collectin-43, all of which have been shown to bind to the C1q receptor found on a wide variety of cells, including macrophages. Both SP-D and SP-A have been shown to enhance oxygen radical production by alveolar macrophages. Although this strongly suggests a direct interaction between SP-D and a specific receptor on alveolar macrophages, it is still unclear whether SP-D binds to the same receptor used by SP-A and/or C1q. Human SP-D was isolated from amniotic fluid and was radiolabelled using 125I. Alveolar macropha...
Surfactant protein D deficiency influences allergic immune responses
Clinical <html_ent glyph="@amp;" ascii="&"/> Experimental Allergy, 2004
Background The collectin surfactant protein D (SP-D) confers protection against pulmonary infection and inflammation. Recent data suggest a role for SP-D in the modulation of allergic inflammation.