Effect of Cyclic AMP on Release of Lysosomal Enzymes from Phagocytes

Weissmann, Gerald; Dukor, P.; Zurier, Robert B.

doi:10.1038/newbio231131a0

Cited by 319 publications

(108 citation statements)

References 24 publications

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“…Many mononuclear-phagocytic functions have been shown to be modulated by changes in intracellular cyclic AMP levels, including migration (Pick, 1972), response to MIF (migration-inhibitory factor) (Koopman et al, 1973) interferoninduced tumoricidal activity (Schultz et al, 1979) plasminogen activator (Vassalli et al, 1976) and lysozomal enzyme secretion (Weissmann et al, 1971), lipopolysaccharide-induced collagenase synthesis (McCarthy et al, 1980) and Fc-receptormediated phagocytosis (Muschel et al, 1977). Since pharmacological agents that increase cyclic AMP (histamine, prostaglandins and phosphodiesterase inhibitors) decrease the synthesis of C2 and other complement components by human monocytes , it appears that cyclic AMP is important in the regulation of this cellular function.…”

Section: Discussionmentioning

confidence: 99%

Cyclic nucleotides and their relationship to complement-component-C2 synthesis by human monocytes

Lappin¹,

Riches²,

Damerau³

et al. 1984

Biochemical Journal

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The time courses of changes in cyclic nucleotide levels in monocytes have been studied. Histamine and prostaglandin E2 (PGE2) produced a rapid rise in cyclic AMP (peak 15min) levels, which returned to normal within 4h, whereas cholera toxin, NaF and phosphodiesterase inhibitors produced slow sustained rises lasting over 24 h. With the exception of isobutylmethylxanthine (1O Mmolh1), none of these reagents altered cyclic GMP levels. oa -Adrenergic and nicotinic cholinergic receptor-ligand interactions and imidazole produced rapid and relatively short-lived falls in cyclic AMP, and rises in cyclic GMP. In contrast, prostaglandin synthetase inhibitors produced delayed but more sustained falls in cyclic AMP but no rises in cyclic GMP. Agents that increased cyclic AMP decreased complement-component-C2 production, and those that decreased cyclic AMP increased C2 production. Agents that increased cyclic GMP alone (ascorbate, nitroprusside and prostaglandin F2a) did not affect C2 production. Antigen-antibody complexes that stimulate C2 synthesis produced falls in cyclic AMP and rises in cyclic GMP similar to those produced by adrenergic and cholinergic ligands. Serum-treated complexes and anaphylatoxins, which inhibited C2 production, were associated with changes in cyclic AMP similar to those produced by histamine and PGE2. These data suggest that there are two transmembrane signals involved in the regulation of C2 production by monocytes. The inhibitory signal is adenylyl cyclase activation. The stimulatory signal is not so obvious, but may be Ca2 + influx, since the time courses of changes in cyclic nucleotides produced by agents that stimulate C2 synthesis are identical, and a, -adrenergic agonists cause the formation of Ca2 + channels.The complement system consists of a series of plasma proteins that plays a major role in host defence. Although hepatocytes are thought to synthesize over 90% of the C3, C6 and factor B that are Abbreviations used: the nomenclature of complement components is that recommended by the World Health Organisation (1968); PGE2, PGF2a, prostaglandins E2

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Section: Discussionmentioning

confidence: 99%

Cyclic nucleotides and their relationship to complement-component-C2 synthesis by human monocytes

Lappin¹,

Riches²,

Damerau³

et al. 1984

Biochemical Journal

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“…In this regard, it is noteworthy that colchicine and vinblastine usually inhibit secretion of prepackaged "granules" but generally fail to affect continuous secretory processes. Thus, colchicine inhibits the secretion of lysosomal enzymes (32) but not the secretion of immunoglobulin from plasma cells (33).…”

Section: Discussionmentioning

confidence: 99%

On the Relation of Products of Activated Lymphocytes to Cell-Mediated Cytolysis

Henney

Gaffney

Bloom

1974

The Journal of Experimental Medicine

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Experiments have been designed to test the hypothesis that soluble mediator production and T-cell-mediated cytotoxicity are necessarily related phenomena, and that soluble mediators may be involved in the mechanism of cytolysis. To this end, agents known to inhibit T-cell-mediated lysis in vitro have been studied for their effects on the production of two lymphocyte-derived mediators, lymphotoxin (LT) and migration inhibitory factor (MIF). A clear dissociation between mediator production and cell-mediated cytolysis was found using inhibitors of protein synthesis. Pactamycin and emetine, in doses of 10–7 M to 10–6 M, suppressed production of MIF and LT with only slight effect on killing of mastocytoma cells by immune T cells. On the other hand colchicine and vinblastine inhibited T-cell-mediated cytolysis in a dose-related manner but had no significant effect on either MIF or LT production, A striking dichotomy was also observed after augmentation of intracellular cyclic 3'5' adenosine monophosphate (cAMP) levels with cholera enterotoxin. Increased cAMP levels were associated with abrogation of direct lytic activity, but were without significant effect on MIF or LT production in guinea pigs or mice. These findings indicate that mediator production and direct lymphocyte-mediated cytolysis can be experimentally dissociated and represent independent cell-mediated immune functions.

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“…Plasminogen activator is a product of activated but not of normal macrophages (Gordon, 1978) and may modulate important interactions between cell-mediated immunity and the clotting system (Hopper, Geczy and Davies, 1981). Release of the cytosol enzyme lactic dehydrogenase reflects cell damage (Weissmann, Dukor and Zurier, 1971). Hydrogen peroxide production is important in the destruction of some intracellular pathogens by macrophages (Murray and Cohn, 1980), a function which can be impaired in tumour-bearing mice (North, Kirstein and Tuttle, 1976;Spitalny, 1980).…”

Section: Introductionmentioning

confidence: 99%

Effects of Tumour Cell Culture Supernatants on Some Biochemical Activities of Macrophages

Nelson

Booth

Nelson

1982

Aust J Exp Biol Med

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Summary The following enzyme activities were measured in cell lysates and supernatants from mouse peritoneal macrophages incubated with products of cultured tumour and other cells: acid phosphatase, β‐D‐glucuronidase, N‐acetyl‐D‐glucosaminidase, muramidase (lysozyme), lactic dehydrogenase (supernatant only) and plasminogen activator (supernatant only). There were no noteworthy changes in enzyme activities. Hydrogen peroxide production by appropriately stimulated mouse and/or guinea‐pig peritoneal exudate macrophages was variably inhibited by supernatants from some tumour cells and some normal cells. Changes in these biochemical activities of macrophages do not appear to be closely related to the anti‐inflammatory activity of tumour cell products.

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Effect of Cyclic AMP on Release of Lysosomal Enzymes from Phagocytes

Cited by 319 publications

References 24 publications

Cyclic nucleotides and their relationship to complement-component-C2 synthesis by human monocytes

Cyclic nucleotides and their relationship to complement-component-C2 synthesis by human monocytes

On the Relation of Products of Activated Lymphocytes to Cell-Mediated Cytolysis

Effects of Tumour Cell Culture Supernatants on Some Biochemical Activities of Macrophages

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