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Expression of surfactant protein D in airways of asthmatics and interleukin-13 modulation of surfactant protein D in human models of airway epithelium.

Xu J, Singhera GK, Dorscheid DR - Respir. Res. (2015)

Bottom Line: Treatment with IL-13 decreased SP-D expression in both ALI cultures (fraction of epithelium 0.21 ± 0.06 vs. 0.62 ± 0.04, p = 0.0005) and monolayer cultures (protein expression fold change 0.62 ± 0.05) of non-asthmatic AEC; however, IL-13 had no significant effect on SP-D expression in monolayer cultures of asthmatic AEC.Experiments with non-asthmatic monolayer cultures indicate IL-13 exert its effect on SP-D through the IL-13 receptor alpha1 and transcription factor STAT6.SP-D is expressed differently in airways of asthmatics relative to that of non-asthmatics.

View Article: PubMed Central - PubMed

ABSTRACT

Background: Surfactant protein D (SP-D), a pattern recognition molecule, has been shown to play roles in host defense such as opsonisation, aggregation of pathogens, and modulation of the inflammatory response. In light of infection-induced exacerbations and damage to the airway epithelium from inflammation, these functions of SP-D make it relevant in the development and pathogenesis of asthma.

Methods: Expression of SP-D was examined in human airway sections and primary airway epithelial cells (AEC) grown in air-liquid interface (ALI) cultures and comparisons were made between those from asthmatic and non-asthmatic donors. ALI cultures of AEC from non-asthmatic donors were examined for SP-D, Mucin 5AC, and cytokeratin-5 expression at different stages of differentiation. Interleukin-13 (IL-13) treatment of airway epithelium and its effect on SP-D expression was studied using ALI and monolayer cultures of primary AEC from non-asthmatic and asthmatic donors.

Results: Airway epithelium of asthmatics, compared to that of non-asthmatics, expressed increased levels of SP-D as demonstrated in airway tissue sections (fraction of epithelium 0.66 ± 0.026 vs. 0.50 ± 0.043, p = 0.004) and ALI cultures (fraction of epithelium 0.50 ± 0.08 vs. 0.25 ± 0.07). SP-D expression decreased as ALI cultures differentiated from 7 days to 21 days (fraction of epithelium 0.62 ± 0.04 to 0.23 ± 0.03, p = 0.004). Treatment with IL-13 decreased SP-D expression in both ALI cultures (fraction of epithelium 0.21 ± 0.06 vs. 0.62 ± 0.04, p = 0.0005) and monolayer cultures (protein expression fold change 0.62 ± 0.05) of non-asthmatic AEC; however, IL-13 had no significant effect on SP-D expression in monolayer cultures of asthmatic AEC. Experiments with non-asthmatic monolayer cultures indicate IL-13 exert its effect on SP-D through the IL-13 receptor alpha1 and transcription factor STAT6.

Conclusions: SP-D is expressed differently in airways of asthmatics relative to that of non-asthmatics. This can have implications on the increased susceptibility to infections and altered inflammatory response in asthmatic patients. Future functional studies on the role of SP-D in asthma can provide better insight into defects in the structure and regulation of SP-D.

No MeSH data available.


Related in: MedlinePlus

Surfactant protein D expression in human airway sections. SP-D expression was examined in sections of airways from non-asthmatic and asthmatic donors via immunohistochemistry, where pink was indicative of positivity [A]. Fraction of total epithelial area positive was quantified using colour segmentation in ImagePro Plus. Expression of SP-D in the airway epithelia of asthmatic donors was significantly higher compared to non-asthmatic donors (n = 11, t-test p = 0.004) [B].
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Fig1: Surfactant protein D expression in human airway sections. SP-D expression was examined in sections of airways from non-asthmatic and asthmatic donors via immunohistochemistry, where pink was indicative of positivity [A]. Fraction of total epithelial area positive was quantified using colour segmentation in ImagePro Plus. Expression of SP-D in the airway epithelia of asthmatic donors was significantly higher compared to non-asthmatic donors (n = 11, t-test p = 0.004) [B].

Mentions: Lung tissue sections obtained from 11 asthmatic and 11 non-asthmatic donors were used to characterize the expression of SP-D in human airways. Immunohistochemistry was performed to study the distribution and relative quantity of SP-D expression. Airways of both asthmatic and non-asthmatic donors expressed SP-D in the cytoplasm of epithelial cells (Figure 1A). When positive staining was expressed as a fraction of total epithelial area, asthmatic airways demonstrated higher SP-D expression (0.66 ± 0.026) compared to non-asthmatic airways (0.50 ± 0.043) (n = 11, p = 0.004, Figure 1B). The presence of SP-D was confirmed in human airways and further, its expression was increased in airways of asthmatics. The non-uniform intensity indicates that SP-D may be expressed more in certain subtypes of airway epithelial cells, specifically undifferentiated basal cells.Figure 1


Expression of surfactant protein D in airways of asthmatics and interleukin-13 modulation of surfactant protein D in human models of airway epithelium.

Xu J, Singhera GK, Dorscheid DR - Respir. Res. (2015)

Surfactant protein D expression in human airway sections. SP-D expression was examined in sections of airways from non-asthmatic and asthmatic donors via immunohistochemistry, where pink was indicative of positivity [A]. Fraction of total epithelial area positive was quantified using colour segmentation in ImagePro Plus. Expression of SP-D in the airway epithelia of asthmatic donors was significantly higher compared to non-asthmatic donors (n = 11, t-test p = 0.004) [B].
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4352233&req=5

Fig1: Surfactant protein D expression in human airway sections. SP-D expression was examined in sections of airways from non-asthmatic and asthmatic donors via immunohistochemistry, where pink was indicative of positivity [A]. Fraction of total epithelial area positive was quantified using colour segmentation in ImagePro Plus. Expression of SP-D in the airway epithelia of asthmatic donors was significantly higher compared to non-asthmatic donors (n = 11, t-test p = 0.004) [B].
Mentions: Lung tissue sections obtained from 11 asthmatic and 11 non-asthmatic donors were used to characterize the expression of SP-D in human airways. Immunohistochemistry was performed to study the distribution and relative quantity of SP-D expression. Airways of both asthmatic and non-asthmatic donors expressed SP-D in the cytoplasm of epithelial cells (Figure 1A). When positive staining was expressed as a fraction of total epithelial area, asthmatic airways demonstrated higher SP-D expression (0.66 ± 0.026) compared to non-asthmatic airways (0.50 ± 0.043) (n = 11, p = 0.004, Figure 1B). The presence of SP-D was confirmed in human airways and further, its expression was increased in airways of asthmatics. The non-uniform intensity indicates that SP-D may be expressed more in certain subtypes of airway epithelial cells, specifically undifferentiated basal cells.Figure 1

Bottom Line: Treatment with IL-13 decreased SP-D expression in both ALI cultures (fraction of epithelium 0.21 ± 0.06 vs. 0.62 ± 0.04, p = 0.0005) and monolayer cultures (protein expression fold change 0.62 ± 0.05) of non-asthmatic AEC; however, IL-13 had no significant effect on SP-D expression in monolayer cultures of asthmatic AEC.Experiments with non-asthmatic monolayer cultures indicate IL-13 exert its effect on SP-D through the IL-13 receptor alpha1 and transcription factor STAT6.SP-D is expressed differently in airways of asthmatics relative to that of non-asthmatics.

View Article: PubMed Central - PubMed

ABSTRACT

Background: Surfactant protein D (SP-D), a pattern recognition molecule, has been shown to play roles in host defense such as opsonisation, aggregation of pathogens, and modulation of the inflammatory response. In light of infection-induced exacerbations and damage to the airway epithelium from inflammation, these functions of SP-D make it relevant in the development and pathogenesis of asthma.

Methods: Expression of SP-D was examined in human airway sections and primary airway epithelial cells (AEC) grown in air-liquid interface (ALI) cultures and comparisons were made between those from asthmatic and non-asthmatic donors. ALI cultures of AEC from non-asthmatic donors were examined for SP-D, Mucin 5AC, and cytokeratin-5 expression at different stages of differentiation. Interleukin-13 (IL-13) treatment of airway epithelium and its effect on SP-D expression was studied using ALI and monolayer cultures of primary AEC from non-asthmatic and asthmatic donors.

Results: Airway epithelium of asthmatics, compared to that of non-asthmatics, expressed increased levels of SP-D as demonstrated in airway tissue sections (fraction of epithelium 0.66 ± 0.026 vs. 0.50 ± 0.043, p = 0.004) and ALI cultures (fraction of epithelium 0.50 ± 0.08 vs. 0.25 ± 0.07). SP-D expression decreased as ALI cultures differentiated from 7 days to 21 days (fraction of epithelium 0.62 ± 0.04 to 0.23 ± 0.03, p = 0.004). Treatment with IL-13 decreased SP-D expression in both ALI cultures (fraction of epithelium 0.21 ± 0.06 vs. 0.62 ± 0.04, p = 0.0005) and monolayer cultures (protein expression fold change 0.62 ± 0.05) of non-asthmatic AEC; however, IL-13 had no significant effect on SP-D expression in monolayer cultures of asthmatic AEC. Experiments with non-asthmatic monolayer cultures indicate IL-13 exert its effect on SP-D through the IL-13 receptor alpha1 and transcription factor STAT6.

Conclusions: SP-D is expressed differently in airways of asthmatics relative to that of non-asthmatics. This can have implications on the increased susceptibility to infections and altered inflammatory response in asthmatic patients. Future functional studies on the role of SP-D in asthma can provide better insight into defects in the structure and regulation of SP-D.

No MeSH data available.


Related in: MedlinePlus