Expression of Flt3-ligand by the endothelial cell

Solanilla, A.; Grosset, Christophe; Lemercier, Claudie; Dupouy, Maryse; Fx, Mahon; Schweitzer, Karin; Reiffers, Josy; Weksler, Babette B.; Ripoche, Jean

doi:10.1038/sj.leu.2401635

Cited by 56 publications

(34 citation statements)

References 53 publications

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“…CCL3 together with matrix metalloproteinases seem to play a critical role in migration of DCs across the endothelial monolayers (Zozulya et al, 2007). CCL3 could also stimulate DCs and endothelial cells production of membrane-bound and soluble Flt3 ligand (Solanilla et al, 2000). Interestingly, inhibition of Flt3 ligand signaling induces apoptosis in human DCs and targeted inhibition of Flt3 significantly improves the course of experimental autoimmune encephalomyelitis, an experimental model for MS (Whartenby et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Dendritic cells are abundant in non-lesional gray matter in multiple sclerosis

Cudrici

Ito

Zafranskaia

et al. 2007

Experimental and Molecular Pathology

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We have analyzed the localization of dendritic cells (DCs) in non-lesional gray matter (NLGM) in comparison to non-lesional white matter (NLWM) and acute or chronic active multiple sclerosis (MS) lesions. Immunohistochemistry was performed on cryostat sections for DCs markers (CD209, CD205, CD83) and other markers for inflammatory cells (CD68, CD8, CD4, CD3, CCR7, CCR5). We found cells expressing CD209 and containing myelin basic protein in both perivascular and parenchymal areas of NLGM. Our findings showing the expression of CD209 + cells in NLGM parenchymal areas are surprising relative to the previous literature which reported the presence of CD209 + DCs only in MS plaque perivascular areas. Although less numerous than CD209 + cells, NLGM cells expressing mature DCs marker CD205 were consistently detected in perivascular cuffs of most lesions. In double labeling experiments, some but not all of the CD209 + cells also expressed CD68 and CCR5. We also found CD209 + cells in close contact with CD3 + lymphocytes suggesting that DCs might contribute to the local activation of pathogenic T cells in the NLGM. Since injury to the NLGM is one of the key factors associated with disability accumulation, targeting DCs may represent a possible new therapeutic approach in MS to prevent disease progression.

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Section: Discussionmentioning

confidence: 99%

Dendritic cells are abundant in non-lesional gray matter in multiple sclerosis

Cudrici

Ito

Zafranskaia

et al. 2007

Experimental and Molecular Pathology

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“…39,[45][46][47][48][49] Since FL is widely expressed in normal tissues and often coexpressed within leukemia cells, aberrantly expressed or overexpressed FLT3 might lead to constitutive dimerization and activation of the receptor. 38,50,51 Finally, mice transplanted with bone marrow transduced with a vector that constitutively expressed human FL have a predisposition to develop leukemia. 52 Thus, several lines of evidence now implicate the FLT3 receptor-ligand combination in leukemogenesis.…”

Section: Flt3 In Leukemiamentioning

confidence: 99%

FLT3: ITDoes matter in leukemia

2003

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FMS-like tyrosine kinase-3 (FLT3), a receptor tyrosine kinase, is important for the development of the hematopoietic and immune systems. Activating mutations of FLT3 are now recognized as the most common molecular abnormality in acute myeloid leukemia, and FLT3 mutations may play a role in other hematologic malignancies as well. The poor prognosis of patients harboring these mutations renders FLT3 an obvious target of therapy. This review summarizes the data on the molecular biology and clinical impact of FLT3 mutations, as well as the therapeutic potential of several small-molecule FLT3 inhibitors currently in development.

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“…28,32,33 Expression of mRNA for the FLT3 ligand (FL) has also been detected in virtually all leukemic-derived cell lines, bone marrow stroma and endothelial cells. 9,[34][35][36] Coexpression of SCF/c-KIT and CSF-1/c-FMS pairs has also been reported in cases of leukemia. [37][38][39] Coexpression of both FLT3 and its ligand by the same leukemia cell suggest a possible autocrine/paracrine/intracrine signaling loop which could contribute to the development or maintenance of leukemia.…”

Section: Introductionmentioning

confidence: 99%