RT Journal Article SR Electronic T1 S122 A role for the bone morphogenetic protein type 2 receptor (bmpr2) in differentiation of the common myeloid progenitor lineage in mice and humans JF Thorax JO Thorax FD BMJ Publishing Group Ltd and British Thoracic Society SP A73 OP A74 DO 10.1136/thoraxjnl-2017-210983.128 VO 72 IS Suppl 3 A1 Crosby, A A1 Hadinnapola, C A1 , A1 Groves, E A1 Moore, S A1 Dunmore, BD A1 Southwood, M A1 Horan, IP A1 Bleda, M A1 Haimel, M A1 Gräf, S A1 Toshner, MR A1 Morrell, NW YR 2017 UL http://thorax.bmj.com/content/72/Suppl_3/A73.2.abstract AB Rationale There is increasing evidence of a link between abnormalities in the myeloid cell lineage and pulmonary arterial hypertension (PAH). Heterozygous mutations in the gene encoding the bone morphogenetic protein type 2 receptor (BMPR2) are the most common genetic cause of PAH. We sought to characterise the impact of the genetic loss/reduction of BMPR2 function in the myeloid lineage in mice and humans, and whether this altered susceptibility to PAH.Methods Mx1-cre mice were crossed with bmpr2flox/flox mice. At approximately 8 weeks of age cre-recombinase was induced with polyinosinic-polycytidylic acid (Poly I:C). Control mice (bmpr2flox/flox mice with no cre) were also induced with Poly I:C. At approximately 16 weeks post-induction mice underwent right-heart catheterisation, exsanguination and tissue was removed for analysis. The spleens were weighed and histology was performed on the femurs. Mouse data are presented as mean ±SEM. In a large cohort of PAH patients with (n=160) and without (n=831) BMPR2 mutations blood count indices were analysed. Data presented as median [IQR].Results 16 weeks after induction of cre-recombinase in Mx1-cre/bmpr2flox/flox mice we observed significant increases (p<0.05) in red blood cells (x106/mm3) (12.7±0.9 compared with 12.1±0.2), haematocrit (%) (64.8±0.7 compared with 62.6±1) and haemoglobin (g/dl) (16±0.9 compared with 15.4±0.2) compared with bmpr2flox/flox mice alone. A significant increase in circulating monocytes (x103/mm3) was also observed (p<0.05) (0.4±0.05 compared with 0.3±0.05). In addition, we identified a significant increase (p<0.05) in megakaryocytes in the femurs (80±10 compared with 17±5) and a significant increase (p<0.01) in the ratio of spleen weight/body weight (0.003±0.0001 compared with 0.002±0.0001) in Mx1-cre/bmpr2flox/flox mice. During right heart catheterisation right ventricular systolic pressures were similar in both groups. In PAH patients significant differences (p<0.05) were seen in haemoglobin (BMPR2 mutation: 162 g/L [151.75–173]) vs. no mutation: 150 g/L [135 – 163]), haematocrit (0.48 [0.45–0.52] vs. 0.44 [0.41–0.48]) and white blood cells (8.8 [7.3–10.4] vs. 8.11 [6.77–9.61]).Conclusions we have identified a role for bmpr2 in the differentiation of the mouse myeloid lineage, which was also confirmed in PAH patients with BMPR2 mutations. BMPR2 appears particularly important in the differentiation of megakaryocyte-erythrocyte lineage.