Mammalian phospholipase C Cell-free preparations from a variety of rat tissues exhibit phospholipase C activities that degrade PtdCho [22-26]. Phospholipase C activities of lysosomal origin with acid pH optima also hydrolyse phosphatidylethanolamine (PtdEtn), phosphatidylinositol and phosphatidylglycerol [22]. PtdChocleaving phospholipases C with alkaline pH optima have been detected in rat brain cytosol [23] and rat liver membranes [24]. Cell-free preparations from endothelial cells also degrade exogenous PtdCho [25,26]. More recently, phospholipases C that utilize PtdCho as substrate have been partially purified from dog heart cytosol [27], bull seminal plasma [28] and promonocytic U937 cells [29]. Utilizing exogenous phospholipids as substrates, these activities exhibit neutral pH optima and do not hydrolyse Vol.

No abstract

No abstract

No abstract

In highly purified human polymorphonuclear leukocyte (PMN) preparations containing less than 0.1% contaminating monocytes, significant amounts of interleukin-8 (IL-8) and small amounts of IL-1 alpha, IL-1 beta, and tumor necrosis factor-alpha (TNF-alpha) were produced by lipopolysaccharide (LPS) stimulation. Contrary to published reports, IL- 6 production could not be detected. IL-10 inhibited the production of IL-1 alpha, IL-1 beta, IL-8, and TNF-alpha in LPS-stimulated PMNs, as it did in human blood mononuclear cell (MNC) preparations enriched in monocytes. Subsequent investigation of cytokine synthesis inhibitory effect of IL-10 on PMNs was focused on IL-8. IL-10 inhibited IL-8 synthesis in a dose-dependent manner and, in this regard, it was more potent than IL-4 and transforming growth factor-beta 1 (TGF-B1). In both MNCs and PMNs, degradation of LPS-induced IL-8 mRNA was enhanced by IL-10. Furthermore, as determined by nuclear run-on assays, IL-10 inhibited LPS-induced transcription of IL-8 gene in MNCs. However, in PMNs, run-on assays could not reliably detect IL-8 gene transcription. These results provide the first evidence that the human peripheral neutrophil is a target for inhibition of cytokine synthesis by IL-10, and that IL-10 acts by affecting both gene transcription and mRNA stability.