Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:6.2.1.7 (
BAL
)
1,977
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Rationale:
The impact of lung insult on the bone marrow (BM) and subsequent disease is unknown.
Objectives:
To study alterations in the BM in response to lung injury/fibrosis and examine their impact on subsequent lung insult.
Methods:
BM cells from control or bleomycin-treated donor mice were transplanted into naive mice, which were subsequently evaluated for bleomycin-induced pulmonary fibrosis. In addition, the effect of prior bleomycin treatment on subsequent fibrosis was examined in wild-type and
B7H3
-knockout mice. Samples from patients with idiopathic pulmonary fibrosis were analyzed for potential clinical relevance of the findings.
Measurements and Main Results:
Recipient mice transplanted with BM from bleomycin-pretreated donors showed significant exacerbation of subsequent fibrosis with increased
B7H3
+
cell numbers and a T-helper cell type 2-skewed phenotype. Pretreatment with a minimally fibrogenic/nonfibrogenic dose of bleomycin also caused exacerbation, but not in
B7H3
-deficient mice. Exacerbation was not observed if the mice received naive BM cell transplant after the initial bleomycin pretreatment. Soluble
B7H3
stimulated BM Ly6C
hi
monocytic cell expansion
in vitro
and caused similar expansion in the lung
in vivo
. Notably, soluble
B7H3
was elevated in plasma of patients with idiopathic pulmonary fibrosis and in
BAL
fluid in those with acute exacerbation. Finally, ST2 deficiency diminished the bleomycin-induced
B7H3
and IL-13 upregulation, suggesting a role for type 2 innate lymphoid cells.
Conclusions:
Pulmonary fibrosis caused significant alterations in BM with expansion and activation of monocytic cells, which enhanced fibrosis when transplanted to naive recipients with potential mediation by a novel role for
B7H3
in the pathophysiology of pulmonary fibrosis in both mice and humans.
...
PMID:Role of B7H3/IL-33 Signaling in Pulmonary Fibrosis-induced Profibrogenic Alterations in Bone Marrow. 3120 14
