A glomerular permeability factor produced by human T cell hybridomas

A glomerular permeability factor produced by human T cell hybridomas. T cell hybridomas derived from the T cells of a patient with minimal change nephrotic syndrome (MCNS) made a glomerular permeability factor (GPF). Sufficient quantities of GPF were available for further analysis and characterization. We obtained four stable clones of human T cell hybridomas which produced a glomerular permeability factor. When this factor was injected intravenously into rats, significant proteinurias were induced, and in normal human lymphocyte culture, GPF enhanced Concanavalin-A (Con-A) induced lymphocyte histogenesis by greater than ten fold. GPF was cytotoxic to tumor cell lines of epithelial origin, but only cytostatic to tumor cells of hematopoietic origin. Electron microscopy studies, with polyethyleneimine (PEI) staining, indicated that GPF induced the changes in the arrangement of PEI particles and partial fusion of glomerular epithelial cells in the rats given this factor intravenously. The molecular weight of GPF were estimated to be between 60,000 and 160,000 daltons. The molecular weight of the factor and its TNF like activity, we speculated that the factor was a lymphokine, like lymphotoxins

Role of nitric oxide in the synthesis of guanidinosuccinic acid, at activator of the N-methyl-d-asparate receptor

Role of nitric oxide in the synthesis of guanidinosuccinic acid, at activator of the N-methyl-d-asparate receptor.BackgroundWe propose that reactive oxygn and arginiosuccinic acid (ASA) form guanidinosuccinic acid (GSA). An alternative to this hypothesis is the so-called guanidine cycle, which consists of a series of hydroxyurea derivatives that serve as intermediates in a pathway leading from urea to GSA. We compare the role of the guanidine cycle to that of nitric oxide (NO) in the synthesis of GSA.MethodsThe members of the guanidine cycle (hydroxyurea, hydroxylamine plus homoserine, L-canaline, and L-canavanine) were incubated with isolated rat hepatocytes. The known NO donors, NOR-2, NOC-7, and SIN-1, were incubated with ASA in vitro. Ornithine, arginine, or citrulline, which increase arginine, a precursor of NO, were incubated with isolated rat hepatocytes. GSA was determined by high-performance liquid chromatography.ResultsNone of guanidine cycle members except for urea formed GSA. SIN-1, which generates superoxide and NO formed GSA, but other simple NO donors, did not. Both carboxy-PTIO, a scavenger, completely inhibited GSA synthesis by SIN-1. GSA formation by SIN-1 reached a maximum at 0.5 mmol/L and decreased at higher concentrations GSA synthesis, stimulated by urea in isolated hepatocytes, was inhibitd by orinithine, arginine, or citrullin with ammonia, but not by ornithine without ammonia, where arginine production is limited.ConclusionGSA is formed ASA and the hydroxyl radical. When arginine increased in hepatocytes, GSA synthesis decreased. These data suggest that increased NO, which results from high concentrations of arginine, or SIN-1, scavanges the hydroxyl radical. This may explain the decreased GSA synthesis in inborn errors of the urea cycle where ASA is decreased, and also the diminished GSA excretion in arginemia