Insulin resistance from chronic kidney disease (CKD) stimulates muscle protein wasting but mechanisms causing this resistance are controversial. To help resolve this, we used microarray analyses to identify initiators of insulin resistance in the muscles of mice with CKD, glucose intolerance, and insulin resistance. CKD raised mRNAs of inflammatory cytokines in muscles and there was a 5.2-fold ...

Interaction between target cell CD47 and the inhibitory macrophage receptor signal regulatory protein (SIRP ) counteracts macrophage phagocytosis of CD47expressing host cells. As platelets also express CD47, we asked whether inhibitory CD47/SIRP signaling regulates normal platelet turnover and clearance of platelets in immune thrombocytopenic purpura (ITP). CD47 / mice had a mild spontaneous th...

MyD-1 (CD172) is a member of the family of signal regulatory phosphatase (SIRP) binding proteins, which is expressed on human CD14 monocytes and dendritic cells. We now show a novel role for MyD-1 in the regulation of the innate immune system by pathogen products such as lipopolysaccharide (LPS), purified protein derivative (PPD), and Zymosan. Specifically, we demonstrate that ligation of MyD-1...

because the 4N1K peptide of thrombospondin-1 was applied at 3 10 mol/l, a concentration that exceeds the thrombospondin-1 concentration in plasma by a factor of 10 to 10 [6]. Correspondingly, Head et al. [7] found that the 4N1K peptide at the very same high concentration (50 g/ml) binds to CD47 without the need to impose a conformational change by e.g. oxidation. Moreover, incubation of RBC wit...

Signal-regulatory proteins (SIRPs) are transmembrane glycoproteins belonging to the immunoglobulin (Ig) superfamily that are expressed in the immune and central nervous systems. SIRPalpha binds CD47 and inhibits the function of macrophages, dendritic cells, and granulocytes, whereas SIRPbeta1 is an orphan receptor that activates the same cell types. A recently identified third member of the SIR...

We have previously proven that human macrophages can phagocytose porcine cells even in the absence of antibody or complement opsonization, indicating that macrophages present a pivotal immunological obstacle to xenotransplantation. A recent report indicates that the signal regulatory protein (SIRP) is a critical immune inhibitory receptor on macrophages, and its interaction with CD47, a ligand ...

Background Adoptive macrophage cell therapy represents a novel approach for cancer immunotherapy. Macrophages engineered to express chimeric antigen receptors (CAR-M) have shown promising pre-clinical results against solid tumors by improving tumor clearance, overall survival and facilitating the remodeling of microenvironment induce potent adaptive immune response. CD47 is well-established che...

Interaction of SIRP with its ligand, CD47, regulates leukocyte functions, including transmigration, phagocytosis, oxidative burst, and cytokine secretion. Recent progress has provided significant insights into the structural details of the distal IgV domain (D1) of SIRP . However, the structural roles of proximal IgC domains (D2 and D3) have been largely unstudied. The high degree of conservati...