Anti-ITGAX Monoclonal antibody, clone 4.0 [PE/Cy5.5®]

Integrin alpha x (ITGAX), a member of theintegrin family, usually serves as a receptor of the extracellular matrix. Recently, accumulating evidence suggests that ITGAX may be involved in angiogenesis in dendritic cells. Herein, we report a direct role of ITGAX in angiogenesis during tumor development. Overexpression of ITGAX in human umbilical vein endothelial cells (HUVECs) enhanced their proliferation, migration, and tube formation and promoted xenograft ovarian tumor angiogenesis and growth. Further study showed that overexpression of ITGAX activated the PI3k/Akt pathway, leading to the enhanced expression of c-Myc, vascular endothelial growth factor-A (VEGF-A), and VEGF receptor 2 (VEGFR2), whereas, the treatment of cells with PI3K inhibitor diminished these effects. Besides, c-Myc was observed to bind to the VEGF-A promoter. By Co-Immunoprecipitation (Co-IP) assay, we manifested the interaction between ITGAX and VEGFR2 or the phosphorylated VEGFR2. Immunostaining of human ovarian cancer specimens suggested that endothelial cells of micro-blood vessels displayed strong expression of VEGF-A, c-Myc, VEGFR2, and the PI3K signaling molecules. Also, overexpression of ITGAX in HUVECs could stimulate the spheroid formation of ovarian cancer cells. Our study uncovered that ITGAX stimulates angiogenesis through the PI3K/Akt signaling-mediated VEGFR2/VEGF-A overexpression during cancer development.

Dendritic cells (DC) are specialized antigen-presenting cells, responsible for peripheral immune responses. Recently, resident brain dendritic cells (bDC) were identified and functionally characterized in the young adult Itgax (CD11c) EYFP+ transgenic mouse brain. In the present study, we describe changes in number, phenotype, and source of bDC in the aging mouse brain. Immunohistochemistry and fluorescent activated cell sorting (FACS) analysis revealed an age-related increase in bDC with a concomitant rise in the expression of immune activation markers MHCII, CD80, and CD86. Quantification of immunolabeled bDC in the cortex, corpus callosum, and cerebellum of the aged brain revealed a 2- to 5-fold increase. In contrast, either no change or a decrease in bDC was noted in regions of adult neurogenesis. Chimeras (wild type host/EYFP+ bone marrow) suggest that the increase of EYFP+ cells in the aging brain is in part due to an accumulation of peripherally derived cells. Collectively, the numerical and phenotypic changes in bDC indicate these cells may serve as an important immune component in the functional and anatomic alterations associated with aging. (C) 2012 Elsevier Inc. All rights reserved.