IndraLab

"Using proximity ligation assay, the authors convincingly demonstrate a physical association between CD11b and CD47 on the retinal MC in the AMD models."

"Therefore, identification of new ways to selectively inhibit CD47-CD11b interactions may offer potential therapeutic approaches to reduce dysregulated PMN trafficking in the gut during pathologic inflammatory diseases without compromising host defense."

"Supportive of our results, there are recent reports suggesting association of CD47 with CD11b in brain mononuclear phagocytes and a macrophage cell line. xref , xref We also report that CD47 association with CD11b/CD18 regulates integrin-dependent PMN adhesion to ligands."

"Given that CD47 has also been shown to physically associate with integrins to regulate adhesive function in different cell types, XREF_BIBR, XREF_BIBR - XREF_BIBR we investigated whether CD47 interacts with CD11b and CD18 in PMN."

"Using PLA, we confirmed results from murine cells indicating close association between CD47 and CD11b in human PMN and HL60 cells."

"Supporting our hypothesis, previous reports have shed light regarding the nature of CD47 and CD11b interaction."

"These results are consistent with interaction between CD47 and CD11b in cis within the PMN plasma membrane."

"A strong positive fluorescent signal was elicited by the combination of human CD47-CD11b Abs as well as the positive control using a combination of CD18-CD11b Abs."

"These results are consistent with interaction between CD47 and CD11b in cis within the PMN plasma membrane."

"We also examined whether interaction between CD47 and CD11b occurs in the same cell using in situ proximal ligation assay (PLA), which can be used to detect different proteins that are in close proximity (within 40 nm) and presumably physically associated."

"With CD47-CD11b association established in human PMN and HL60 cells, we tested whether CD47 regulates CD11b/CD18 activation on these leukocytes."

"As observed in xref , the function blocking mAb miap301 that recognizes the IgV domain of CD47 xref reduced PMN chemotaxis in vitro , suggesting a blockade of the interaction CD47-CD11b at the extracellular side."

"We also examined whether interaction between CD47 and CD11b occurs in the same cell using in situ-proximal ligation assay (PLA), which can be used to detect different proteins that are in close proximity (within 40 nm) and presumably physically associated."

"Using CD47 chimeric molecules, others have reported that the extracellular IgV and first transmembrane domains of CD47 are required for β 1 -dependent adhesion of T-cells to VCAM-1 and similarly for α IIb β 3 and α v β 3 activation in platelets and in an ovarian cancer cell line, respectively. xref , xref , xref Furthermore, we hypothesized that lipid and cholesterol composition of the membrane is an important factor for stabilizing CD47-CD11b interactions, as previous work has demonstrated that CD47 engages α v β 3 integrin and Gi proteins in lipid rafts domains to form signaling complexes. xref It is possible that the CD47-CD11b complex is already formed in the membrane of secondary granules as CD11b/CD18 and CD47 are within the membranes of these organelles. xref In addition to in cis interactions, it is well appreciated that PMN-expressed CD47 can also bind in trans with thrombospondins, and SIRPα expressed by other cells."

"34 It is possible that the CD47 and CD11b complex is already formed in the membrane of secondary granules as CD11b and CD18 and CD47 are within the membranes of these organelles."

"Supporting our hypothesis, previous reports have shed light regarding the nature of CD47 and CD11b interaction."