Evaluation of role of G-CSF in the production, survival, and release of neutrophils from bone marrow into circulation

Abstract

In steady-state hematopoiesis, G-CSF (granulocyte-colony stimulating factor) regulates the level of neutrophils in the bone marrow and blood. In this study, we have exploited the availability of G-CSFdeficient mice to evaluate the role of G-CSF in steady-state granulopoiesis and the release of granulocytes from marrow into circulation. The thymidine analogue bromodeoxyuridine (BrdU) was used to label dividing bone marrow cells, allowing us to follow the release of granulocytes into circulation. Interestingly, the labeling index and the amount of BrdU incorporated by blast cells in bone marrow was greater in G-CSF-deficient mice than in wild-type mice. In blood, 2 different populations of BrdU-positive granulocytes, BrdU bright and BrdU dim , could be detected. The kinetics of release of the BrdU bright granulocytes from bone marrow into blood was similar in wild-type and G-CSF-deficient mice; however, BrdU dim granulocytes peaked earlier in G-CSF-deficient mice. Our findings suggest that the mean transit time of granulocytes through the postmitotic pool is similar in G-CSF-deficient and control mice, although the transit time through the mitotic pool is reduced in G-CSF-deficient mice. Moreover, the reduced numbers of granulocytes that characterize G-CSF-deficient mice is primarily due to increased apoptosis in cells within the granulocytic lineage. Collectively, our data suggest that at steady state, G-CSF is critical for the survival of granulocytic cells; however, it is dispensable for trafficking of granulocytes from bone marrow into circulation. (Blood. 2002;100:854-861)

Functional and molecular characterization of NOS isoforms in rat neutrophil precursor cells

“…Although eNOS mediated stem cell migration to the ischemic myocardium via upregulation of SDF-1 has also been demonstrated (34,57). G-CSF, a key regulator of neutrophil homeostasis, triggers bonemarrow neutrophils to release matrix metalloproteinase-9 (MMP9), to mobilize progenitor cells (58,59). G-CSF production from stromal cells is regulated by interleukin-17 (IL-17) released from a subset of T cells.…”

G-CSF-initiated myeloid cell mobilization and angiogenesis mediate tumor refractoriness to anti-VEGF therapy in mouse models

“…2; SI Methods). Both G-CSF (25) and Bv8 (16,19) have been shown to induce peripheral mobilization of CD11b ϩ Gr1 ϩ cells. Tumor analysis revealed a greater frequency of CD11b ϩ Gr1 ϩ cells in refractory tumors compared with sensitive ones (Fig.…”

Caracterização do efeito da crotoxina sobre a funcionalidade dos neutrófilos da medula óssea

“…A seguir, são liberados para a circulação sanguínea onde permanecem até serem removidos por apoptose. A sua vida média na circulação sanguínea varia de acordo com a espécie, em camundongos é de aproximadamente 10 horas (Basu et al, 2002), enquanto que em humanos esse tempo pode ser estendido por 5,4 dias (Pillay et al, 2010). Entretanto, em resposta a agentes estimulatórios, tais como endotoxina ou citocinas pró-inflamatórias, a vida média dessas células aumenta (Chilvers et al, 2000;Gomez et al, 2008).…”

“…Essas células são temporariamente armazenadas no pool de reserva da medula óssea e, a seguir, são liberadas para a circulação sanguínea onde permanecem por aproximadamente 10 horas (Basu et al, 2002 concentrações dessa toxina pelo período de 1 hora (Lima et al, 2012). Nesse estudo, a concentração 0,08 μg/mL foi a mais efetiva, assim, os ensaios in vitro para análise da funcionalidade dos neutrófilos da medula óssea foram realizados utilizando essa concentração de CTX e o mesmo tempo de incubação.…”