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

Abstract

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

Acute versus chronic administration of phosphodiesterase inhibitors on allergen‐induced pulmonary cell influx in sensitized guinea‐pigs

“…Theophylline and IBMX have been shown to inhibit the generation of potent eosinophil chemoattractants such as PAF and complement C2 from human monocytes (Lappin et al, 1984). The activation and proliferation of T-lymphocytes which are believed to play an important role in eosinophil recruitment into the airways (Corrigan & Kay, 1989) can also be inhibited by mixed type III/IV PDE inhibitors (Robicsek et al, 1991;Schudt et al, 1992) and by type IV PDE inhibitors (Averill & Kammer, 1985;Banner & Page, 1994b).…”

Lack of effect of zaprinast on methacholine‐induced contraction and inositol 1,4,5‐trisphosphate accumulation in bovine tracheal smooth muscle

“…Aliquots (250pl) of the neutralized tissue extracts were diluted 2 fold in 100mm sodium acetate (pH6.2) and acetylated by the consecutive addition of triethylamine (10lp) and acetic anhydride (5 pl). Cyclic GMP levels were then measured by radioimmunoassay as described by Brooker et al (1979) and Lappin et al (1984). In brief, 100,l of acetylated sample were added to 25 p1 guanosine-3', 5'-cyclic monophosphate, 2-0-succinyl 3-[125I]-iodotyrosine methyl ester in 0.1% BSA (approx.…”

Modulation by interferons of the expression of monocyte complement genes

“…Monocyte monolayers were prepared in 24-well Linbro tissueculture plates and the cells were cultured in RPMI 1640 containing 10% (v/v) ABS (RPMI/ABS) at 37°C in a humidified air/CO2 (19: 1) atmosphere (Lappin et al, 1984). After 3 days the culture medium was removed and replaced with fresh medium consisting of RPMI 1640 containing 20 % (v/v) FCS (RPMI/FCS) and incubated under the same conditions for a further day before any experiments were started.…”