THE IMPACT OF SLEEP DEPRIVATION IN THE BONE MARROW PROGENITORS AND THE ROLE OF ANGIOTENSIN-CONVERTING ENZYME

Sleep deprivation (SD) affects immune system response and regulation of the hematopoietic stem cells (HSC). However, how SD modifies hematopoiesis is not fully elucidated. The tetrapeptide Ac-SDKP, which is degraded by angiotensin converting-enzyme (ACE) in the bone marrow, is a natural inhibitor of the HSC proliferation. In the present study, we test the hypothesis that SD decreases ACE activity and affects the differentiation of HSC via AcSDKP. Male C57BL/6 mice (N=6/group) were subjected to SD during 72 h and to a sleep recovery (SR) period of 10 days. Whole blood and cells from the bone marrow were collected for quantification of HSC, hematopoietic progenitors, mature cells and ACE. White blood cells, erythrocytes and platelets did not differ in the peripheral blood between groups. Lymphoid progenitors were significantly reduced in the bone marrow of the SD (P<0.01). After the SR period, the number of myeloid progenitors increased compared to control. Interestingly, the lymphoid progenitors remain reduced during SR. ACE activity was reduced in SD (2.6 ±0.5) and remains decreased in SR (2.9 ±0.5) compared to control (4.0 ±1 AU/min/mg prot. P=0.03). To further examine whether AcSDKP explains a direct effect on the number of colony-forming unit (CFU), we quantified the number of myeloid and lymphoid progenitor-CFU in the presence or absence of AcSDKP in the bone marrow cells. AcSDKP reduced the number of CFU-Pre B of SD compared to control. The number of lymphoid-CFU returns to basal levels and myeloid-CFU remains reduced in SR. We concluded that: SD decreases ACE and the number of lymphoid B progenitors and its ability to form colonies in murine bone marrow; SR for 10 days is insufficient to return the lymphoid progenitors. ACE/AcSDKP axis is important mediator in the HSC maturation during SD. These data support further the concept of the ACE/AcSDKP axis contributes to the impairment of the immune response in SD. FAPESP (2012/02123-0), CNPq and Associação de Fundo e Incentivo à Pesquisa (AFIP).