Mice with restricted ablation of 5-HT_2BRs to BM are resistant to pulmonary hypertension. (A) WT mice transplanted with BM cells from WT or 5-HT_2B^−/− (WT_WT, WT_KO, respectively) and 5-HT_2B^−/− knock-out (KO) mice transplanted with BM cells from 5-HT_2B^−/− or WT (KO_KO, KO_WT, respectively) were exposed to progressive hypoxia (20%-10% for 3 weeks). (B) Pulmonary arterial pressure as assessed by RVSP increased in mice bearing WT BM either in WT (WT_WT) or 5-HT_2B^−/− (KO_WT) background. Conversely, mice with 5-HT_2B^−/− BM into WT (WT_KO) or 5-HT_2B^−/− (KO_KO) background did not show any RVSP increase. (C) Immunohistochemistry of c-Kit and 5-HT_2BR. Staining was performed with antibodies against 5-HT_2BR (pink; rabbit polyclonal AbCam) or against c-Kit (blue; rat monoclonal AbCam). Sections were analyzed under ×200 original magnification using a Zeiss Axiophot microscope with inbuilt camera (Carl Zeiss). A 20×/0.30 air objective was used. Images were acquired using a Zeiss Axiocam camera and Axiovision Version 3.1 software. Scale bars represent 50 μm. (D) Lung 5-HT_2BR expression (Bmax) increased in mice bearing WT BM not only in WT (WT_WT) but also in 5-HT_2B^−/− (KO_WT) background. Conversely, not only mice with 5-HT_2B^−/− BM into 5-HT_2B^−/− (KO_KO), but also in WT (WT_KO) background did not show any change in lung 5-HT_2BR expression compared with controls WT (18 fmoles/mg prot) or full 5-HT_2B^−/− (less than 5 fmoles/mg prot). (E) Similarly, the pulmonary perivascular c-kit⁺ BM derived progenitor cell recruitment induced by hypoxia was higher in mice with WT BM to WT (WT_WT) or 5-HT_2B^−/− (KO_WT) background as revealed by quantification of the immuno-labeling. Values are means ± SEM (n = 12, P < .05). Lines are normoxic values. Any statistical difference by 1-way ANOVA followed by Bonferroni posthoc test is indicated by ***P < .001.