Extramedullary hematopoiesis is dysregulated in histamine-free histidine decarboxylase knockout (HDC-/-) mice

In this study we investigated the role of histamine on the extramedullary hematopoiesis. Male histidine decarboxylase knockout (HDC-/-) mice and wild-type mice were used (n = 5/group). Groups of mice received sublethal total-body gamma irradiation at a single dose of 4 Gy. Spleen cells were studied at different time points post-irradiation by flow cytometry, colony forming unit (CFU) assay, and real-time PCR. For statistical analysis Student's t test, ANOVA, and Holm-Sidak post-hoc test were used. By day 14 after irradiation, spleen cell counts increased almost eightfold in wild-type and not even fourfold in HDC-/- mice (P < 0.01). The proliferative capacity and interleukin-3 signaling of stem cells were impaired in HDC-/- mice. STAT5 mRNA expression was decreased in granulocyte-myeloid colonies by 72.9 +/- A 8.6% (P < 0.001), compared to the wild-type. The absence of histamine adversely affects splenic hematopoiesis via direct and indirect mechanisms.