Journal
INTERNATIONAL JOURNAL OF HEMATOLOGY
Volume 113, Issue 3, Pages 348-361Publisher
SPRINGER JAPAN KK
DOI: 10.1007/s12185-020-03051-0
Keywords
Histamine; Histidine decarboxylase (HDC); Nitrogen-containing bisphosphonate (NBP); Extramedullary erythropoiesis; Vascular adhesion molecule 1 (VCAM-1)
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Funding
- JSPS KAKENHI from the Ministry of Education, Culture, Sports, Science and Technology of Japan [17K17089]
- Grants-in-Aid for Scientific Research [17K17089] Funding Source: KAKEN
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Histamine may affect the hematopoietic microenvironments of the bone marrow and spleen by changing hematopoiesis-related factors in NBP-induced extramedullary hematopoiesis.
Histidine decarboxylase (HDC), a histamine synthase, is expressed in various hematopoietic cells and is induced by hematopoietic cytokines such as granulocyte colony-stimulating factor (G-CSF). We previously showed that nitrogen-containing bisphosphonate (NBP)-treatment induces extramedullary hematopoiesis via G-CSF stimulation. However, the function of HDC in NBP-induced medullary and extramedullary hematopoiesis remains unclear. Here, we investigated changes in hematopoiesis in wild-type and HDC-deficient (HDC-KO) mice. NBP treatment did not induce anemia in wild-type or HDC-KO mice, but did produce a gradual increase in serum G-CSF levels in wild-type mice. NBP treatment also enhanced Hdc mRNA expression and erythropoiesis in the spleen and reduced erythropoiesis in bone marrow and the number of vascular adhesion molecule 1 (VCAM-1)-positive macrophages in wild-type mice, as well as increased the levels of hematopoietic progenitor cells and proliferating cells in the spleen and enhanced expression of bone morphogenetic protein 4 (Bmp4), CXC chemokine ligand 12 (Cxcl12), and hypoxia inducible factor 1 (Hif1) in the spleen. However, such changes were not observed in HDC-KO mice. These results suggest that histamine may affect hematopoietic microenvironments of the bone marrow and spleen by changing hematopoiesis-related factors in NBP-induced extramedullary hematopoiesis.
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