Nitric oxide-induced murine hematopoietic stem cell fate involves multiple signaling proteins, gene expression, and redox modulation.

There are a growing number of reports showing the influence of redox modulation in cellular signaling. Although the regulation of hematopoiesis by reactive oxygen species (ROS) and reactive nitrogen species (RNS) has been described, their direct participation in the differentiation of hematopoietic stem cells (HSCs) remains unclear. In this work, the direct role of nitric oxide (NO(•)), a RNS, in the modulation of hematopoiesis was investigated using two sources of NO(•) , one produced by endothelial cells stimulated with carbachol in vitro and another using the NO(•)-donor S-nitroso-N-acetyl-D,L-penicillamine (SNAP) in vivo. Two main NO(•) effects were observed: proliferation of HSCs-especially of the short-term HSCs-and its commitment and terminal differentiation to the myeloid lineage. NO(•)-induced proliferation was characterized by the increase in the number of cycling HSCs and hematopoietic progenitor cells positive to BrdU and Ki-67, upregulation of Notch-1, Cx43, PECAM-1, CaR, ERK1/2, Akt, p38, PKC, and c-Myc. NO(•)-induced HSCs differentiation was characterized by the increase in granulocytic-macrophage progenitors, granulocyte-macrophage colony forming units, mature myeloid cells, upregulation of PU.1, and C/EBPα genes concomitantly to the downregulation of GATA-3 and Ikz-3 genes, activation of Stat5 and downregulation of the other analyzed proteins mentioned above. Also, redox status modulation differed between proliferation and differentiation responses, which is likely associated with the transition of the proliferative to differentiation status. Our findings provide evidence of the role of NO(•) in inducing HSCs proliferation and myeloid differentiation involving multiple signaling.

Açäo dos raios X corpo total sobre os neutrófilos do sangue periférico em primata Cebus apella (macaco prego) / Effects of whole-body X-radiation on the neutrophils of the peripheral blood of the primate Cebus apella (weeping capuchin)

Amostras de sangue periférico foram obtidas de cinco primatas Cebus apella (macaco prego), antes e após exposiçäo aos raios X corpo inteiro, na dose única de 25,8 mC/kg (100R). Parte das amostras foi utilizada para a contagem global de cariosquizes e o restante para a realizaçäo de extensöes sanguíneas e submetidas à coloraçäo de Wright e aos seguintes métodos citoquímicos: ácido periódico Schiff (PAS) para a identificaçäo de glicogênio, Sudan black B para a detecçäo de fosfolipídios e o-toluidina-água oxigenada para a demonstraçäo da mieloperoxidase. Com o método de Wright foram observadas aos 1, 3 e 6 dias após exposiçäo à radiaçäo, alteraçöes nucleares e citoplasmáticas. Após aplicaçäo dos métodos citoquímicos acima referidos, foram observados, de modo geral, nos mesmos períodos de tempo após irradiaçäo: alteraçäo no padräo de distribuiçäo dos grânulos de glicogênio, grânulos mieloperoxidase positivos e sudanófilos de neutrófilos. No que diz respeito a cariosquizes, constatou-se um aumento dos mesmos após 1 dia, persistindo até o 3§ dia após irradiaçäo. Noventa dias após, näo foi observada nenhuma alteraçäo acima referida

Effects of whole-body x-irradiation on the peripheral blood of primate Cebus apella

The effects of ionizing radiation on the peripheral blood elements of primate Cebus apella were examined after a single 25.8mC/kg (100 R) dose of whole-body X-ray. We determined the number of white blood cells,neutrophils, osophils, basophils,lymphocytes,monocytes anderythrocytes up to 90 days after exposure of 5 animals. Hemoglobin content and microhematocrit were also determined. Under these experimental conditions, the total number of leukocytes was reduced from 9440/mm***3 to 5660/mm***3 on day6, mainly because of a decrease inthe lymphocyte population from 5843.2/mm***3 to 2349.0/mm***3 on day 6. No significant differences were observed in the values of erythrocytes, neutrophils,eosinophils,basophils,monocytes,hemoglobin content and microhematocrit. All hematological parameters studied returned tonormal values by day 90 after a single irradiation dose of 100R

Effects of whole-body X-irradiation on the peripheral blood of primate Cebus apella.

The effects of ionizing radiation on the peripheral blood elements of primate Cebus apella were examined after a single 25.8 mC/kg (100 R) dose of whole-body X-ray. We determined the number of white blood cells, neutrophils, eosinophils, basophils, lymphocytes, monocytes and erythrocytes up to 90 days after exposure of 5 animals. Hemoglobin content and microhematocrit were also determined. Under these experimental conditions, the total number of leukocytes was reduced from 9440/mm3 to 5660/mm3 on day 6, mainly because of a decrease in the lymphocyte population from 5843.2/mm3 to 2349.0/mm3 on day 6. No significant differences were observed in the values of erythrocytes, neutrophils, eosinophils, basophils, monocytes, hemoglobin content and microhematocrit. All hematological parameters studied returned to normal values by day 90 after a single irradiation dose of 100 R.

Variacao numerica dos lisossomas nas celulas do tubulo contorcido proximal do rim de camundongo submetido a diferentes doses do raio X. / Numerical change of cell lysosomes of the proximal convoluted tubules of mice kidneys submitted to different X-ray doses

Comparando-se o numero de lisossomas nas celulas do tubulo contorcido proximal de rim de camundongo, antes e apos irradiacao com diferentes doses de exposicao corpo inteiro aos raios X, constatou-se uma diminuicao estatisticamente significante em 72 horas

The thickness of the glomerular basement membrane in irradiated and unirradiated Wistar rats and C-57 BL mice of different age groups.

In both Wistar rats and C-57 BL mice, the thickness of the glomerular basement membrane increases progressively with age. This change, which can be measured in cohorts of manageable size, produces a measurement of biological age--if one accepts the assumption that it correlates with the viability of the organism that exhibit it. Whole-body exposure to x-rays has no observable influence on this age-related change.

Estimation of bone marrow injury through biopsies from whole-body irradiated monkeys (Cebus apela).

In the x-irradiated mammal, the ratio erythrocytes/nucleated cells is positively correlated with the radiation dose. In the present report, this correlation is used to estimate, by means of marrow biopsies, the radiation dose received by whole-body exposed monkeys.