Surfactant protein D alters allergic lung responses in mice and human subjects

Brandt, Eric B.; Mingler, Melissa K.; Stevenson, Michelle D.; Wang, Ning; Hershey, Gurjit K. Khurana; Whitsett, Jeffrey A.; Rothenberg, Marc E.

doi:10.1016/j.jaci.2008.02.011

Cited by 54 publications

(53 citation statements)

References 41 publications

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“…It is also notable that serum SP-D is increased in COPD as compared to controls [33]. As higher SP-D levels are linked with 'T' allele [22,29], our finding of the association of COPD with 'T' allele of rs721917 is consistent with this observation.…”

Section: Discussionsupporting

confidence: 88%

“…Another reason for the differences in results could be variation in the genetic backgrounds of subjects. This phenomenon has been well described by Brandt and coworkers [22]. They used the same protocol on black and white subjects but found the 'Met allele' to be associated with atopy and asthma in only black subjects.…”

Section: Discussionsupporting

confidence: 67%

“…Rs721917 is associated with increased susceptibility to tuberculosis [18] Influenza A virus [19] infection, allergic rhinitis [20], COPD [21], respiratory syncitial virus (RSV) infection in infants [17], atopy [22] and blood levels of SP-D [23]. Rs2243639, on the other hand, has been associated with ulcerative colitis [24] and risk of respiratory syncytial virus infection (RSV) in neonates [25].…”

Section: Introductionmentioning

confidence: 99%

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SP-D Polymorphisms and the Risk of COPD

et al. 2012

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Abstract.Introduction: There are limited data linking serum levels of surfactant protein D, its genetic polymorphisms to the risk of Chronic Obstructive Pulmonary Disease (COPD). Objectives: We sought to investigate these relationships using a case control study design. Methods: Post bronchodilator values of FEV1/FVC <0.7 were used to diagnose COPD patients (n = 115). Controls were healthy subjects with normal spirometry (n = 106) Single nucleotide polymorphisms (rs721917, rs2243639, rs3088308) were genotyped using polymerase chain reaction (PCR) and restriction analysis. Serum SP-D levels were measured using a specific immunoassay. Results: Allele 'A' at rs3088308 (p < 0.00, B = −0.41) and 'C' allele at rs721917 (p = 0.03; B = −0.30) were associated with reduced serum SP-D levels. Genotype 'T/T' at rs721917 was significantly associated with risk of COPD (p = 0.01). Patients with repeat exacerbations had significantly higher serum SP-D even after adjusting for genetic factors. Conclusions: We report for the first time that rs3088308 is an important factor influencing systemic SP-D levels and confirm the previous association of rs721917 to the risk of COPD and serum SP-D levels.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionsupporting

confidence: 67%

Section: Introductionmentioning

confidence: 99%

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SP-D Polymorphisms and the Risk of COPD

et al. 2012

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“…Clara cells have previously been reported to secrete various factors that are involved in the protection and defence mechanisms of the lung. For example, CC10 and SP-D secreted by Clara cells play a protective role in asthma by inhibiting Th2 responses [10,30]. Pro-inflammatory mediators, such as acidic mammalian chitinase, are upregulated in Clara cells during Th2 inflammation and their inhibition ameliorates inflammation [31].…”

Section: Discussionmentioning

confidence: 99%

Clara cells drive eosinophil accumulation in allergic asthma

Sonar

Ehmke²,

Marsh³

et al. 2011

Eur Respir J

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Development of allergic asthma is a complex process involving immune, neuronal and tissue cells. In the lung, Clara cells represent a major part of the ''immunomodulatory barrier'' of the airway epithelium.To understand the contribution of these cells to the inflammatory outcome of asthma, disease development was assessed using an adjuvant-free ovalbumin model. Mice were sensitised with subcutaneous injections of 10 mg endotoxin-free ovalbumin in conjunction with naphthaleneinduced Clara cell depletion.Clara epithelial cell depletion in the lung strongly reduced eosinophil influx, which correlated with decreased eotaxin levels and, moreover, diminished the T-helper cell type 2 inflammatory response, including interleukin (IL)-4, IL-5 and IL-13. In contrast, airway hyperresponsiveness was increased. Further investigation revealed Clara cells as the principal source of eotaxin in the lung.These findings are the first to show that Clara airway epithelial cells substantially contribute to the infiltration of eotaxin-responsive CCR3+ immune cells and augment the allergic immune response in the lung. The present study identifies Clara cells as a potential therapeutic target in inflammatory lung diseases such as allergic asthma.

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“…SP-D also binds to several allergens, thereby modifying allergic responses in the lung [15][16][17]. In murine asthma models, SP-D attenuates allergen-induced eosinophilia and T H 2 cytokine production, resulting in suppression of airway hyper-responsiveness and remodeling [18]. SP-D levels in bronchoalveolar lavage fluid (BALF) have been shown to correlate with the severity of asthma, airway smooth muscle mass, and reticular basement membrane thickness [19]; serum SP-D concentrations are associated with the degree of bronchial inflammation in allergic patients.…”

Section: Introductionmentioning

confidence: 99%

The Biomarker Salivary SP-D May Indicate Small Airway Inflammation and Asthma Exacerbation

Okazaki¹,

Murai²,

Kidoguchi³

et al. 2017

J Investig Allergol Clin Immunol

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Background: Noninvasive and child-friendly biomarkers are important tools for understanding the various phenotypes of childhood asthma. Objective: The aim of this study was to examine the usefulness of salivary surfactant protein (SP) D in assessing the pathophysiology of childhood asthma. Methods: We measured salivary concentrations of SP-D and forced oscillation technique (FOT) indexes in 19 healthy controls and 21 asthmatic children. Regression equations for the predictive values of FOT indexes were generated from healthy controls. We analyzed the correlations between salivary SP-D concentration and percentages of the predictive values of FOT indexes, as well as the severity of exacerbation. Results: We found that salivary SP-D levels were higher in asthmatic children than in healthy controls. In the asthmatic children, salivary SP-D levels correlated with the percentages of predicted differences in resistance between 5 Hz and 20 Hz (%R5-R20), which represented the resistance of peripheral airways, and with the severity of asthma exacerbation. Conclusion: Salivary SP-D may reflect asthmatic inflammation in peripheral small airways and may be a useful marker for monitoring the degree of exacerbation in childhood asthma.

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Surfactant protein D alters allergic lung responses in mice and human subjects

Cited by 54 publications

References 41 publications

SP-D Polymorphisms and the Risk of COPD

SP-D Polymorphisms and the Risk of COPD

Clara cells drive eosinophil accumulation in allergic asthma

The Biomarker Salivary SP-D May Indicate Small Airway Inflammation and Asthma Exacerbation

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