Anti-ITGAX Monoclonal antibody, clone 4.0 [Alexa Fluor® 700]

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.

Sepsis is a life-threatening syndrome caused by abnormal host immune responses against bacterial infection. Although innate immune cells are known to be important in the pathogenesis of sepsis, how their activation is regulated during sepsis remains incompletely understood. Here, we examined the role of the inhibitory immunoreceptor CD300a, which is expressed on various types of myeloid cells, in the pathogenesis of sepsis induced by cecal ligation and puncture (CLP). To this end, we used mice in which CD300a was specifically deleted on mast cells (MCs; Cd300a(fl/fl)Mcpt5-Cre), dendritic cells (DCs; Cd300a(fl/fl)Itgax-Cre), or macrophages and neutrophils (Cd300a(fl/fl)Lyz2-Cre). We show that mice with CD300a-deleted MCs or DCs but not macrophages survived significantly longer than did control Cd300a(fl/fl) mice. In addition, whereas neutrophil recruitment into the peritoneal cavity was increased within 1 h after CLP in mice with CD300a-deleted MCs, peritoneal neutrophils did not increase in number until the 12 h time point in mice with CD300a-deficient DCs. These results indicate that CD300a on MCs and DCs regulates neutrophil recruitment into the peritoneal cavity after CLP.