| First Author | Kim K | Year | 2015 |
| Journal | Blood | Volume | 126 |
| Issue | 16 | Pages | 1952-64 |
| PubMed ID | 26333777 | Mgi Jnum | J:230675 |
| Mgi Id | MGI:5763528 | Doi | 10.1182/blood-2014-10-605261 |
| Citation | Kim K, et al. (2015) NOX2 is critical for heterotypic neutrophil-platelet interactions during vascular inflammation. Blood 126(16):1952-64 |
| abstractText | Platelet-leukocyte interactions on activated endothelial cells play an important role during microvascular occlusion under oxidative stress conditions. However, it remains poorly understood how neutrophil-platelet interactions are regulated during vascular inflammation. By using intravital microscopy with mice lacking nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 (NOX2) and their bone marrow chimera, we demonstrated that NOX2 from both hematopoietic and endothelial cells is crucial for neutrophil-platelet interactions during tumor necrosis factor alpha-induced venular inflammation. Platelet NOX2-produced reactive oxygen species (ROS) regulated P-selectin exposure upon agonist stimulation and the ligand-binding function of glycoprotein Ibalpha. Furthermore, neutrophil NOX2-generated ROS enhanced the activation and ligand-binding activity of alphaMbeta2 integrin following N-formyl-methionyl-leucyl phenylalanine stimulation. Studies with isolated cells and a mouse model of hepatic ischemia/reperfusion injury revealed that NOX2 from both platelets and neutrophils is required for cell-cell interactions, which contribute to the pathology of hepatic ischemia/reperfusion injury. Platelet NOX2 modulated intracellular Ca(2+) release but not store-operated Ca(2+) entry (SOCE), whereas neutrophil NOX2 was crucial for SOCE but not intracellular Ca(2+) release. Different regulation of Ca(2+) signaling by platelet and neutrophil NOX2 correlated with differences in the phosphorylation of AKT, ERK, and p38MAPK. Our results indicate that platelet and neutrophil NOX2-produced ROS are critical for the function of surface receptors essential for neutrophil-platelet interactions during vascular inflammation. |
