Abstract
Systemic fibrosis can be induced in humans with gadolinium-based contrast, and cumulative doses correlate with severity. Bone marrow-derived fibrocytes accumulate in the dermis.Whether target organs liberate chemokines to recruit these fibrocytes or whether fibrocytes are stimulated to home to the affected tissue is unknown. Transgenic (tagged) donor rats were treated with gadolinium-based contrast. Bone marrow was obtained from diseased animals and age-matched controls. Rats with subtotal nephrectomies were lethally irradiated and underwent salvage transplantation with either the contrast-näýve or contrast-exposed bone marrow. Groups were randomly assigned to control or contrast treatment. Contrast treatment led to dermal fibrosis, and this was exacerbated in recipients of contrast-exposed marrow. Fibronectin, C-C chemokine receptors (CCRs)2 and 7, and oxidative stress were all increased in skin from contrast-treated animals-all parameters more severe in recipients of contrast-treated animals. The respective ligands, monocyte chemoattractant protein and C-C motif ligand 19, were both elevated in skin from contrast-treated animals. Coadministration of gadolinium-based contrast and a CCR2 inhibitor reduced the severity of skin disease as well as dermal cellularity. The functional role of chemokines in the effects of gadolinium-based contrast was further confirmed in in situ coculture studies using neutralizing CCR2 antibodies. These data implicate dermal liberation of specific chemokines in the recruitment of circulating bone marrow-derivedcells.Thedisease isaugmentedbybonemarrowexposure to contrast,whichexplainswhymultiple exposures correlate with severity.-Drel, V. R., Tan, C., Barnes, J. L., Gorin, Y., Lee, D.-Y.,Wagner, B. Centrality of bone marrow in the severity of gadolinium-based contrast-induced systemic fibrosis.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 3026-3038 |
| Number of pages | 13 |
| Journal | FASEB Journal |
| Volume | 30 |
| Issue number | 9 |
| DOIs | |
| State | Published - Sep 1 2016 |
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Keywords
- CCR2
- Chemokine CCL2
- NADPH oxidase
- Nephrogenic fibrosing dermopathy
- Skin diseases
ASJC Scopus subject areas
- Biotechnology
- Biochemistry
- Molecular Biology
- Genetics
Cite this
Centrality of bone marrow in the severity of gadolinium-based contrast-induced systemic fibrosis. / Drel, Viktor R.; Tan, Chunyan; Barnes, Jeffrey L.; Gorin, Yves; Lee, Doug Yoon; Wagner, Brent.
In: FASEB Journal, Vol. 30, No. 9, 01.09.2016, p. 3026-3038.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Centrality of bone marrow in the severity of gadolinium-based contrast-induced systemic fibrosis
AU - Drel, Viktor R.
AU - Tan, Chunyan
AU - Barnes, Jeffrey L.
AU - Gorin, Yves
AU - Lee, Doug Yoon
AU - Wagner, Brent
PY - 2016/9/1
Y1 - 2016/9/1
N2 - Systemic fibrosis can be induced in humans with gadolinium-based contrast, and cumulative doses correlate with severity. Bone marrow-derived fibrocytes accumulate in the dermis.Whether target organs liberate chemokines to recruit these fibrocytes or whether fibrocytes are stimulated to home to the affected tissue is unknown. Transgenic (tagged) donor rats were treated with gadolinium-based contrast. Bone marrow was obtained from diseased animals and age-matched controls. Rats with subtotal nephrectomies were lethally irradiated and underwent salvage transplantation with either the contrast-näýve or contrast-exposed bone marrow. Groups were randomly assigned to control or contrast treatment. Contrast treatment led to dermal fibrosis, and this was exacerbated in recipients of contrast-exposed marrow. Fibronectin, C-C chemokine receptors (CCRs)2 and 7, and oxidative stress were all increased in skin from contrast-treated animals-all parameters more severe in recipients of contrast-treated animals. The respective ligands, monocyte chemoattractant protein and C-C motif ligand 19, were both elevated in skin from contrast-treated animals. Coadministration of gadolinium-based contrast and a CCR2 inhibitor reduced the severity of skin disease as well as dermal cellularity. The functional role of chemokines in the effects of gadolinium-based contrast was further confirmed in in situ coculture studies using neutralizing CCR2 antibodies. These data implicate dermal liberation of specific chemokines in the recruitment of circulating bone marrow-derivedcells.Thedisease isaugmentedbybonemarrowexposure to contrast,whichexplainswhymultiple exposures correlate with severity.-Drel, V. R., Tan, C., Barnes, J. L., Gorin, Y., Lee, D.-Y.,Wagner, B. Centrality of bone marrow in the severity of gadolinium-based contrast-induced systemic fibrosis.
AB - Systemic fibrosis can be induced in humans with gadolinium-based contrast, and cumulative doses correlate with severity. Bone marrow-derived fibrocytes accumulate in the dermis.Whether target organs liberate chemokines to recruit these fibrocytes or whether fibrocytes are stimulated to home to the affected tissue is unknown. Transgenic (tagged) donor rats were treated with gadolinium-based contrast. Bone marrow was obtained from diseased animals and age-matched controls. Rats with subtotal nephrectomies were lethally irradiated and underwent salvage transplantation with either the contrast-näýve or contrast-exposed bone marrow. Groups were randomly assigned to control or contrast treatment. Contrast treatment led to dermal fibrosis, and this was exacerbated in recipients of contrast-exposed marrow. Fibronectin, C-C chemokine receptors (CCRs)2 and 7, and oxidative stress were all increased in skin from contrast-treated animals-all parameters more severe in recipients of contrast-treated animals. The respective ligands, monocyte chemoattractant protein and C-C motif ligand 19, were both elevated in skin from contrast-treated animals. Coadministration of gadolinium-based contrast and a CCR2 inhibitor reduced the severity of skin disease as well as dermal cellularity. The functional role of chemokines in the effects of gadolinium-based contrast was further confirmed in in situ coculture studies using neutralizing CCR2 antibodies. These data implicate dermal liberation of specific chemokines in the recruitment of circulating bone marrow-derivedcells.Thedisease isaugmentedbybonemarrowexposure to contrast,whichexplainswhymultiple exposures correlate with severity.-Drel, V. R., Tan, C., Barnes, J. L., Gorin, Y., Lee, D.-Y.,Wagner, B. Centrality of bone marrow in the severity of gadolinium-based contrast-induced systemic fibrosis.
KW - CCR2
KW - Chemokine CCL2
KW - NADPH oxidase
KW - Nephrogenic fibrosing dermopathy
KW - Skin diseases
UR - http://www.scopus.com/inward/record.url?scp=84990821405&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84990821405&partnerID=8YFLogxK
U2 - 10.1096/fj.201500188R
DO - 10.1096/fj.201500188R
M3 - Article
C2 - 27221979
AN - SCOPUS:84990821405
VL - 30
SP - 3026
EP - 3038
JO - FASEB Journal
JF - FASEB Journal
SN - 0892-6638
IS - 9
ER -