leukotriene-b4 and Renal-Insufficiency

Release of prostaglandin E2 (PGE2) and leukotrien B4 (LTB4) in vitro by resting and PHA-stimulated peripheral blood mononuclear cells (PBMNC) in the presence of three concentrations of myoinositol (30, 300, 600 micromol/l) was investigated.. We examinated 10 uremic patients on regular hemodialysis treatment and 10 healthy subjects (control group).. Release of PGE2 and LTB4 by resting and PHA-stimulated PBMNC was significantly lower in the presence of myoinositol in concentrations generally obserwed in the blood serum of chronic uraemic patients on regular hemodialysis treatment (600 micromol/l) in both investigated groups, while it remained unchanged in the presence of myoinositol in the concentration observed in normal blood serum (30 micromol/l).. The results seem to indicate that myoinositol, in the concentrations found in uremic blood serum, may possibly exert antiinflammatory actions.

Topics: Adult; Dinoprostone; Female; Humans; In Vitro Techniques; Inositol; Leukocytes, Mononuclear; Leukotriene B4; Male; Renal Insufficiency; Uremia

Leukotriene B(4) (LTB(4)) is a potent chemoattractant and activator of both granulocytes and macrophages. The actions of LTB(4) appear to be mediated by a specific G protein-coupled receptor (GPCR) BLT1, originally termed BLT (Yokomizo, T., T. Izumi, K. Chang, Y. Takuwa, and T. Shimizu. 1997. Nature. 387:620-624). Here, we report the molecular cloning of a novel GPCR for LTB(4), designated BLT2, which binds LTB(4) with a Kd value of 23 nM compared with 1.1 nM for BLT1, but still efficiently transduces intracellular signaling. BLT2 is highly homologous to BLT1, with an amino acid identity of 45.2%, and its open reading frame is located in the promoter region of the BLT1 gene. BLT2 is expressed ubiquitously, in contrast to BLT1, which is expressed predominantly in leukocytes. Chinese hamster ovary cells expressing BLT2 exhibit LTB(4)-induced chemotaxis, calcium mobilization, and pertussis toxin-insensitive inhibition of adenylyl cyclase. Several BLT1 antagonists, including U 75302, failed to inhibit LTB(4) binding to BLT2. Thus, BLT2 is a pharmacologically distinct receptor for LTB(4), and may mediate cellular functions in tissues other than leukocytes. BLT2 provides a novel target for antiinflammatory therapy and promises to expand our knowledge of LTB(4) function. The location of the gene suggests shared transcriptional regulation of these two receptors.

Topics: Amino Acid Sequence; Animals; Arthritis, Rheumatoid; Asthma; Base Sequence; Cell Line; CHO Cells; Cloning, Molecular; Cricetinae; DNA, Complementary; Humans; Inflammatory Bowel Diseases; Leukotriene B4; Mice; Molecular Sequence Data; Psoriasis; Receptors, Leukotriene B4; Renal Insufficiency; Sequence Homology, Amino Acid; Signal Transduction; Tissue Distribution