The leukocyte adhesion molecule DNAM-1 (CD226) is a member of the immunoglobulin superfamily and constitutively expressed on the majority of CD4+ and CD8+ T lymphocytes, natural killer (NK) cells, monocytes/macrophages, and a subset of B lymphocytes. The poliovirus receptor (PVR; CD155) and its family member nectin 2 (CD112) have recently been identified as the ligands for DNAM-1. Interaction of DNAM-1 with the ligands induces NK cell- and CD8+ T cell-mediated cytotoxicity and cytokine secretion. However, in vivo function of the receptor-ligand interaction has remained unclear. Here, we identified murine DNAM-1 and PVR homologues that physically and functionally bind each other. We demonstrated that ligand binding of murine DNAM-1 induced a costimulatory signal in antigen-specific CD8+ T cells. These results should provide a useful animal model to explore a role of DNAM-1 in immune responses in vivo.
The previous slide-glass type system could simultaneously detect reactive and highly reactive oxygen species, i.e., superoxide radicals (O2−·) and hypochlorite ions (OCl−) elicited from leucocytes in sample blood, but had some drawbacks, i.e., signal noise from air-flow stirring, potential biohazard risks, etc. because of open samples placed on a slide glass. We overcame these drawbacks by adopting a fluidic-chip container in a new system, which resulted in higher sensitivity and more stable measurements. Using the new system, we conducted a pilot study on nominally healthy volunteers to find whether or not the monitored activities of leukocytes can distinguish more or less unhealthy conditions from healthy ones. At first, healthy volunteers of both genders and of various ages showed that the fluctuation magnitudes (%) of O2−· and OCl− were nearly similar to each other and to that of the neutrophil count fluctuation. These parameters sometimes exceeded the healthy fluctuation range. By comparing these large fluctuations with the data of an inflammation marker C-reactive protein (CRP), the neutrophil count fluctuation and the timings/symptoms of abnormalities found in questionnaire, we could gain information suggesting the factors causing the large fluctuations. The new system could detect bodily abnormalities earlier than CRP or self-aware symptoms.
The relationships between changes in myocardial uptake of metaiodobenzylguanidine (MIBG) and those in circulating catecholamines and cardiac function after treatment of phaeochromocytoma and neuroblastoma were evaluated. Iodine-123 or iodine-131 MIBG scintigraphy was performed before and after surgical resection and/or chemotherapy for primary tumours in nine patients with phaeochromocytoma and 13 patients with neuroblastoma. Changes in myocardial MIBG uptake after treatment were estimated by the heart-to-upper mediastinum (H/M) uptake ratios on the images obtained 24 h after MIBG injection, which were compared with serum levels of noradrenaline (NA) and adrenaline (A). Cardiac function was assessed by echocardiography, with measurements of the left ventricular ejection fraction (LVEF). Before treatment, eight patients with phaeochromocytoma and three with neuroblastoma showed poor myocardial MIBG uptake, with highly elevated circulating NA and A. Echocardiography, however, did not show cardiac dysfunction in these patients with the exception of two patients with phaeochromocytoma. With normalization of NA and A levels after treatment, all of these patients except for the two with persistent cardiac dysfunction showed restoration of myocardial MIBG uptake. The H/M ratios increased significantly after treatment in both patient groups, i.e. with phaeochromocytoma and with neuroblastoma (P<0.0001 and P<0.05, respectively), and these ratios correlated inversely with circulating NA and A before and after treatment. By contrast, there was no significant correlation between H/M ratios and LVEF in these two groups. These results indicate that suppression of myocardial MIBG uptake usually may not be related to cardiac dysfunction and may be reversible following normalization of excess catecholamine levels after treatment in patients with neuroadrenergic tumours. However, the suppression may persist in the presence of catecholamine-induced cardiac dysfunction. The assessment of myocardial MIBG uptake can be a helpful adjunct in monitoring the normalization of circulating catecholamine levels and also in identifying the presence of cardiac dysfunction in treated patients with neuroadrenergic tumours.
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