Hematologic effects of flt3 ligand in vivo in mice

Abstract

We have investigated the effects of in vivo treatment with flt3 ligand (FL) on murine hematopoiesis, including mobilization of progenitors into the peripheral blood (PB). Mice were injected once daily with 10 micrograms recombinant human FL for 15 days. On days 3, 5, 8, 10, 15, and 22, mice were killed and analyzed for the number of leukocytes and colony-forming units (CFU) in bone marrow (BM), spleen, and PB. Splenic and PB cellularity increased with time in FL-treated mice. In the spleen, there was an increase in B cells, myeloid cells, and nucleated erythroid cells; in the PB, there was an increase in lymphocytes, granulocytes, and monocytic cells. The maximal number of CFU in the BM was observed after 3 days of FL treatment, giving 3.7- and 7.3-fold increases in CFU-granulocyte-macrophage (CFU-GM) and CFU-granulocyte, erythrocyte, monocyte, megakaryocyte (CFU-GEMM), respectively, compared with mouse serum albumin (MSA)-treated controls. After 8 days of FL treatment, there was a maximal 123- and 108-fold increase in splenic CFU-GM and CFU-GEMM, respectively. The maximal number CFU-GM and CFU- GEMM were seen in PB on day 10, with 537- and 585-fold increases, respectively. Burst-forming units-erythroid (BFU-E) increased in the same time frame as those of CFU-GM and CFU-GEMM in BM, spleen, and PB, although the magnitude was not as great. Primitive day-13 CFU-spleen (CFU-S) and phenotypically defined stem cells were also mobilized into the PB of FL-treated mice with similar kinetics and magnitude to that of CFU-GM and CFU-GEMM. We conclude from these studies that FL, when administered as a single agent, is a potent mobilizer of hematopoietic progenitors into the PB.

Serum FLT‐3 ligand in a busulphan‐induced model of chronic bone marrow hypoplasia in the female CD‐1 mouse

“…Studies in the mouse (Brasel et al 1996) have shown that daily administration of FL at 10 lg ⁄ mouse for 15 days by i.p. injection promotes lymphopoiesis with peripheral blood and spleen WBC counts increasing significantly.…”

“…injection promotes lymphopoiesis with peripheral blood and spleen WBC counts increasing significantly. The experiments of Brasel et al (1996) also showed that the administration of FL had a positive effect on the number of HSCs. Indeed, HSCs characterized as lin -, Sca-1 + and c-Kit + , were found in higher numbers in the bone marrow, spleen and peripheral blood of FL-treated mice.…”

Mucosal CD8α+ DC, with a plasmacytoid phenotype, induce differentiation and support function of T cells with regulatory properties

“…once daily for 10 consecutive days, a process known to expand all DC subsets without activation. 23 All DC subsets investigated in this report are present in mice that have not been treated with Flt3-L (Table 1). A single-cell suspension was prepared from the spleen, mesenteric lymph nodes (MLN), Peyer's patches (PP) and peripheral lymph nodes (PLN) (inguinal, popliteal, axillary, brachial and cervical) of treated mice by mechanical disruption of tissue (n 10 mice/group).…”

“…Chinese hamster ovary (CHO)-derived human Flt3-ligand (Flt3L) was produced and puri®ed as described previously. 23 Puri®ed and biotin-labelled anti-IL-4, anti-IL-10 and anti-IFN-g antibodies were purchased from BD Pharmingen.…”

Serum Cytokine Profiling in Cats with Acute Idiopathic Cystitis

“…The receptor for this ligand (Flt3) is expressed in hematopoietic progenitor cells and is crucial for development of dendritic cells and enhances production of lymphoid progenitors. [35][36][37] Flt3L has been implicated as a pro-inflammatory factor in the pathogenesis of a variety of inflammatory diseases. [38][39][40] It also has been shown to have a protective, anti-inflammatory role in some animal models.…”