Detection of a uteroglobin-like phospholipase A2 inhibitory protein in the circulation of rabbits.
Uteroglobin (UG) or blastokinin is a steroid-dependent low molecular weight secretory protein in the rabbit. This protein has many immunomodulatory properties. Recently, UG has been reported to be a potent phospholipase A2 (E.C. 3.1.1.4) inhibitor and this property may explain, at least in part, the immunomodulatory/antiinflammatory effects of this protein. Although UG has been detected in many reproductive and non-reproductive tissues of the rabbit it has not been reported in the circulation of this animal. Here, we present biochemical and immunochemical evidence for the presence of a low molecular weight circulating protein with progesterone binding and phospholipase A2 inhibitory properties similar to rabbit uterine UG. The major organs which contribute UG-like protein in circulation seem to be the tracheobronchial tree and to a lesser extent the uterus. The concentration of this protein is much higher in the vicinity of these organs as compared to peripheral circulation. Phospholipase A2 (PLA2)-catalyzed reaction is the major pathway of arachidonic acid production from cell membrane phospholipids. Arachidonic acid participates in the stimulation of guanylate cyclase, adenylate cyclase, protein kinase C and release of calcium from intracellular stores. These processes are thought to be involved in cellular signal transduction. Arachidonic acid is also essential for eicosanoid synthesis and many eicosanoids (e.g. prostaglandins, leukotrienes, etc.) are proinflammatory. Thus, the UG-like protein by inhibiting PLA2 may play a vital role in the regulation of cellular signal transduction, control of inflammation and platelet aggregation.
Kikukawa
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Section on Developmental Genetics, National Institute of Child Health and Human Development, Bethesda, MD 20892.
Mukherjee
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D000818:Animals; D015153:Blotting, Western; D002850:Chromatography, Gel; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006023:Glycoproteins / Q000097:blood*; D010740:Phospholipases / Q000037:antagonists & inhibitors*; D010741:Phospholipases A / Q000037:antagonists & inhibitors*; D054467:Phospholipases A2; D011233:Precipitin Tests; D011374:Progesterone / Q000378:metabolism / Q000494:pharmacology; D011485:Protein Binding; D011667:Pulmonary Veins; D011817:Rabbits; D011863:Radioimmunoassay; D014598:Uteroglobin / Q000097:blood*; D014599:Uterus / Q000098:blood supply; D014680:Veins
D006023:Glycoproteins; D011374:Progesterone; D014598:Uteroglobin; D010740:Phospholipases; D010741:Phospholipases A; D054467:Phospholipases A2