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Pericytes contribute to airway remodeling in a mouse model of chronic allergic asthma.

Johnson JR, Folestad E, Rowley JE, Noll EM, Walker SA, Lloyd CM, Rankin SM, Pietras K, Eriksson U, Fuxe J - Am. J. Physiol. Lung Cell Mol. Physiol. (2015)

Bottom Line: Unexpectedly, we found that pharmacological inhibition of PDGFRβ signaling in the context of chronic aeroallergen exposure led to exacerbated lung dysfunction and airway smooth muscle thickening.This process was exacerbated in animals treated with CP-673451.The results indicate that perturbed PDGF-BB/PDGFRβ signaling and pericyte accumulation in the airway wall may contribute to airway remodeling in chronic allergic asthma.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Biochemistry and Biophysics, Matrix Division, Division of Vascular Biology, Karolinska Institutet, Stockholm, Sweden; Leukocyte Biology Section, National Heart and Lung Institute, Sir Alexander Fleming Building, Imperial College London, London, United Kingdom; and jill.johnson@imperial.ac.uk.

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Pericyte localization was assessed in ear biopsies (A and B) and in the lungs (C and D) of wild-type and Tg(Cspg4-DsRed.T1)1Akik/J saline control mice by direct imaging of the DsRed fluorescent signal. The identity of DsRed-positive cells in the lungs was assessed by colocalization of the signal in α-SMA+ (E–H) and NG2-expressing (I–L) pericytes in the pulmonary blood vessels (BV). Immunostaining of lung sections from DsRed-NG2 transgenic mice for α-SMA (green), DsRedNG2+ pericytes (red), CD31 (white), and cell nuclei (DAPI; blue) was performed in saline control (M–O) and HDM-exposed (P–R) mice (i.n. 5 days/wk for 5 wk). White arrows indicate DsRed-NG2+ cells present in the lung parenchyma (E, F, M), black arrow indicates DsRed-NG2+/α-SMA+ cells present in the airway smooth muscle (ASM) bundles (P), and arrowheads indicate microvessel-associated DsRedNG2+ cells (F, I). Scale bars 25 μm (A–R).
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Figure 7: Pericyte localization was assessed in ear biopsies (A and B) and in the lungs (C and D) of wild-type and Tg(Cspg4-DsRed.T1)1Akik/J saline control mice by direct imaging of the DsRed fluorescent signal. The identity of DsRed-positive cells in the lungs was assessed by colocalization of the signal in α-SMA+ (E–H) and NG2-expressing (I–L) pericytes in the pulmonary blood vessels (BV). Immunostaining of lung sections from DsRed-NG2 transgenic mice for α-SMA (green), DsRedNG2+ pericytes (red), CD31 (white), and cell nuclei (DAPI; blue) was performed in saline control (M–O) and HDM-exposed (P–R) mice (i.n. 5 days/wk for 5 wk). White arrows indicate DsRed-NG2+ cells present in the lung parenchyma (E, F, M), black arrow indicates DsRed-NG2+/α-SMA+ cells present in the airway smooth muscle (ASM) bundles (P), and arrowheads indicate microvessel-associated DsRedNG2+ cells (F, I). Scale bars 25 μm (A–R).

Mentions: To further study the effect of HDM on pericyte localization in the mouse airways, we used transgenic NG2DsRedBAC reporter mice [Tg(Cspg4-DsRed.T1)1Akik/J]. These mice express the red fluorescent protein DsRed.T1 under the control of the mouse NG2 (Cspg4) promoter and were thus used to interrogate whether pericytes accumulate in the ASM following chronic HDM exposure (Fig. 7). The genotype of the mice was confirmed by observation of ear biopsies under a fluorescent microscope; bright red NG2+ cells were observable surrounding the base of hair follicles in transgene-bearing mice (Fig. 7, A and B). We were able to observe DsRed-NG2 cells in the walls of large vessels (Fig. 7, D–H), and DsRed-NGS cells were also positive for NG2 by antibody-mediated staining (Fig. 7, I–L). DsRed-NG2 cells were absent from the ASM bundles of saline control mice (Fig. 7, M–O), whereas clusters of DsRed-NG2 cells were clearly visible within the ASM bundles of mice exposed to HDM for 5 wk (Fig. 7, P–R).


Pericytes contribute to airway remodeling in a mouse model of chronic allergic asthma.

Johnson JR, Folestad E, Rowley JE, Noll EM, Walker SA, Lloyd CM, Rankin SM, Pietras K, Eriksson U, Fuxe J - Am. J. Physiol. Lung Cell Mol. Physiol. (2015)

Pericyte localization was assessed in ear biopsies (A and B) and in the lungs (C and D) of wild-type and Tg(Cspg4-DsRed.T1)1Akik/J saline control mice by direct imaging of the DsRed fluorescent signal. The identity of DsRed-positive cells in the lungs was assessed by colocalization of the signal in α-SMA+ (E–H) and NG2-expressing (I–L) pericytes in the pulmonary blood vessels (BV). Immunostaining of lung sections from DsRed-NG2 transgenic mice for α-SMA (green), DsRedNG2+ pericytes (red), CD31 (white), and cell nuclei (DAPI; blue) was performed in saline control (M–O) and HDM-exposed (P–R) mice (i.n. 5 days/wk for 5 wk). White arrows indicate DsRed-NG2+ cells present in the lung parenchyma (E, F, M), black arrow indicates DsRed-NG2+/α-SMA+ cells present in the airway smooth muscle (ASM) bundles (P), and arrowheads indicate microvessel-associated DsRedNG2+ cells (F, I). Scale bars 25 μm (A–R).
© Copyright Policy - open-access
Related In: Results  -  Collection

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Figure 7: Pericyte localization was assessed in ear biopsies (A and B) and in the lungs (C and D) of wild-type and Tg(Cspg4-DsRed.T1)1Akik/J saline control mice by direct imaging of the DsRed fluorescent signal. The identity of DsRed-positive cells in the lungs was assessed by colocalization of the signal in α-SMA+ (E–H) and NG2-expressing (I–L) pericytes in the pulmonary blood vessels (BV). Immunostaining of lung sections from DsRed-NG2 transgenic mice for α-SMA (green), DsRedNG2+ pericytes (red), CD31 (white), and cell nuclei (DAPI; blue) was performed in saline control (M–O) and HDM-exposed (P–R) mice (i.n. 5 days/wk for 5 wk). White arrows indicate DsRed-NG2+ cells present in the lung parenchyma (E, F, M), black arrow indicates DsRed-NG2+/α-SMA+ cells present in the airway smooth muscle (ASM) bundles (P), and arrowheads indicate microvessel-associated DsRedNG2+ cells (F, I). Scale bars 25 μm (A–R).
Mentions: To further study the effect of HDM on pericyte localization in the mouse airways, we used transgenic NG2DsRedBAC reporter mice [Tg(Cspg4-DsRed.T1)1Akik/J]. These mice express the red fluorescent protein DsRed.T1 under the control of the mouse NG2 (Cspg4) promoter and were thus used to interrogate whether pericytes accumulate in the ASM following chronic HDM exposure (Fig. 7). The genotype of the mice was confirmed by observation of ear biopsies under a fluorescent microscope; bright red NG2+ cells were observable surrounding the base of hair follicles in transgene-bearing mice (Fig. 7, A and B). We were able to observe DsRed-NG2 cells in the walls of large vessels (Fig. 7, D–H), and DsRed-NGS cells were also positive for NG2 by antibody-mediated staining (Fig. 7, I–L). DsRed-NG2 cells were absent from the ASM bundles of saline control mice (Fig. 7, M–O), whereas clusters of DsRed-NG2 cells were clearly visible within the ASM bundles of mice exposed to HDM for 5 wk (Fig. 7, P–R).

Bottom Line: Unexpectedly, we found that pharmacological inhibition of PDGFRβ signaling in the context of chronic aeroallergen exposure led to exacerbated lung dysfunction and airway smooth muscle thickening.This process was exacerbated in animals treated with CP-673451.The results indicate that perturbed PDGF-BB/PDGFRβ signaling and pericyte accumulation in the airway wall may contribute to airway remodeling in chronic allergic asthma.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Biochemistry and Biophysics, Matrix Division, Division of Vascular Biology, Karolinska Institutet, Stockholm, Sweden; Leukocyte Biology Section, National Heart and Lung Institute, Sir Alexander Fleming Building, Imperial College London, London, United Kingdom; and jill.johnson@imperial.ac.uk.

Show MeSH
Related in: MedlinePlus