Impairment of immunogenicity by antigen presentation in liposomes made from dimyristoylphosphatidyl‐ethanolamine linked to the secretion of prostaglandins by macrophages

Bakouche, Quahid; David, F.; Gerlier, Denis

doi:10.1002/eji.1830171225

Cited by 24 publications

(10 citation statements)

References 24 publications

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“…In addition, several drugs which block the transport of proteins along the classical secretory pathway cause an increase, rather than an inhibition, in IL-1,B secretion. These findings, together with the observations that IL-1: is not found in the ER by morphological and biochemical criteria (Bakouche et al, 1987;Singer et al, 1988) and is not glycosylated at Asn123, demonstrate that IL-1: is not translocated into the ER.…”

Section: Discussionmentioning

confidence: 58%

“…Both forms of IL-1 lack a typical signal sequence, either N-terminal or internal (Auron et al, 1984;March et al, 1985). In agreement with this, immunoelectron microscopy (Singer et al, 1988) and subcellular fractionation Bakouche et al, 1987) studies failed to demonstrate IL-1 molecules in the ER and in the Golgi apparatus, raising the question of how they can be released by the producer cells. Here we show that IL-i1$ is selectively secreted by human activated monocytes via a novel pathway of secretion.…”

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confidence: 89%

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A novel secretory pathway for interleukin-1 beta, a protein lacking a signal sequence.

et al. 1990

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Interleukin 1 (IL‐1) is a major soluble mediator of inflammation. Two human IL‐1 genes, alpha and beta, have been isolated, which encode polypeptides with only 20‐30% amino acid sequence homology. Unlike most secreted proteins, the two cytokines do not have a signal sequence, an unexpected finding in view of their biological role. Here we show that IL‐1 beta is actively secreted by activated human monocytes via a pathway of secretion different from the classical endoplasmic reticulum‐‐Golgi route. Drugs which block the intracellular transport of IL‐6, of tumour necrosis factor alpha and of other secretory proteins do not inhibit secretion of IL‐1 beta. Secretion of IL‐1 beta is blocked by methylamine, low temperature or serum free medium, and is increased by raising the culture temperature to 42 degrees C or by the presence of calcium ionophores, brefeldin A, monensin, dinitrophenol or carbonyl cyanide chlorophenylhydrazone. IL‐1 beta is contained in part within intracellular vesicles which protect it from protease digestion. In U937 cells large amounts of IL‐1 beta are made but none is secreted. In these cells IL‐1 beta is not found in the vesicular fraction, and all the protein is accessible to protease digestion. This suggests that intracellular vesicles that contain IL‐1 beta are part of the protein secretory pathway. We conclude that IL‐1 beta is released by activated monocytes via a novel mechanism of secretion which may involve translocation of intracellular membranes and is increased by stress conditions.

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Section: Discussionmentioning

confidence: 58%

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confidence: 89%

A novel secretory pathway for interleukin-1 beta, a protein lacking a signal sequence.

et al. 1990

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“…Further, fusion between Na+-rich endosomes and intracellular vesicles may represent a simple mechanism for lowering K+ concentrations in intracellular compartments. In this context, intracellular pro-IL-iP (Giri et al, 1985; Bayne et al, 1986;Bakouche et al, 1987;Singer et al, 1988) appears to be present in trypsin-resistant vesicles (Rubartelli et al, 1990). K+ may itself influence the movement of vesicles, akin to its inhibitory effect on endocytosis (Larkin et al, 1983;McVey Ward et al, 1990;Ilondo et al, 1991;Hansen et al, 1993).…”

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confidence: 99%

Potassium-inhibited processing of IL-1 beta in human monocytes.

et al. 1995

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Agents that deplete cells of K+ without grossly disrupting the plasma membrane were found to stimulate the cleavage of pro‐interleukin (IL)‐1 beta to mature IL‐1 beta. Agents examined in this study included staphylococcal alpha‐toxin and gramicidin, both of which selectively permeabilize plasma membranes for monovalent ions, the ionophores nigericin and valinomycin, and the Na+/K+ ATPase inhibitor ouabain. K+ depletion by brief hypotonic shock also triggered processing of pro‐IL‐1 beta. The central role of K+ depletion for inducing IL‐1 beta maturation was demonstrated in cells permeabilized with alpha‐toxin: processing of pro‐IL‐1 beta was totally blocked when cells were suspended in medium that contained high K+, but could be induced by replacing extracellular K+ with Na+, choline+ or sucrose. To test whether K+ flux might also be important in physiological situations, monocytes were stimulated with lipopolysaccharide (LPS) for 1‐2 h to trigger pro‐IL‐1 beta synthesis, and transferred to K(+)‐rich medium. This maneuver totally suppressed IL‐1 beta maturation. Even after 16 h, however, removal of K+ from the medium resulted in rapid processing and export of IL‐1 beta. Ongoing export of mature IL‐1 beta from cells stimulated with LPS for 2‐6 h could also be arrested by transfer to K(+)‐rich medium. Moreover, a combination of two K+ channel blockers inhibited processing of IL‐1 beta in LPS‐stimulated monocytes. We hypothesize that K+ movement and local K+ concentrations directly or indirectly influence the action of interleukin‐1 beta‐converting enzyme (ICE) and, possibly, of related intracellular proteases.

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“…However, hopeful are only those procedures, in which the isolated subunit proteins are integrated into corpuscular, multimolecular structures, such as liposomes or ISCOMs (Naylor et al 1982;Perrin et al 1984;.Bakouche et al 1987;Tan et al 1989;Morein et a1. 1987;Trudel et al 1987).…”

Section: Resultsmentioning

confidence: 99%

“…Enhancement of antigenicity of proteins, incorporated into ISCOMs or liposomes, was reported by Boudreault and Thibodeau (1985), Bakouche et a!. (1987), Trudel et al (1987), Elguink (1989), Tan et al (1989), Brynestad et al (1990), Gregoriadis (1990) and Lovgren and Morein (1991).…”

mentioning

confidence: 82%

Incorporation of Bovine Herpesvirus 1 Protein Subunits into Large Unilamellar and Multilamellar Liposomes

Hampl¹,

Štěpánek²,

Fränz³

et al. 1992

Acta Vet. Brno

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Hampl J., J. StC!panek, J. FranZ Acta vet. Bmo, 61, 1992: 29-36. Virus proteins, obtained by the treatment of purified bovine herpesvirus 1 with detergents, were incorporated into large unilamellar (LUV) and multilamellar (MLV) liposomes. Their antigenicity was compared with that of virus proteins adsorbed onto LUV surface in mice. Both antibody levels and dynamics of antibody responses, examined by ELISA and RIA, confirmed a marked immunostimulatory effect of the liposomes. The most pronounced antibody responses were observed in animals injected with virus proteins incorporated into LUV, prepared from egg phospholipid, or adsorbed onto their surface. BOfJine herpesT.Jirus 1, fJirus proteins, antibody response, large unilamellar liposomes, multilamellar liposomesOne of the current innovation trends in the production of vaccines against virus diseases of farm animals is the development of subunit vaccines. The principle consists in the selection from the whole complex of virus structural proteins of those, which elicit an immune response providing the protection of vaccinates (protective antigens). The question whether the proteins are obtained by degradation of complete virus particles, propagated by conventional methods, or are prepared in vitro by techniques of molecular biology, is irrelevaIit.A common drawback, limiting the immediate use of such proteins, is their rather weak immunogenicity, which is much lower than that of the same proteins as a part of complete virion structures. All attempts to compensate for this drawback by the use of current non-specific immunostimulants or adiuvants have failed (Dougan 1985;Rowland 1986;Zanetti et al. 1987; Liu and Cepica 1990).A certain effect was evident, however, when the protein subunits were incorporated back into multimolecular, corpuscular structures, such as ISCOMs (immunity stimulating complex), or various types of liposomes. In both cases, the size and shape of the particles resemble those of virions.Enhancement of antigenicity of proteins, incorporated into ISCOMs or liposomes, was reported by

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Impairment of immunogenicity by antigen presentation in liposomes made from dimyristoylphosphatidyl‐ethanolamine linked to the secretion of prostaglandins by macrophages

Cited by 24 publications

References 24 publications

A novel secretory pathway for interleukin-1 beta, a protein lacking a signal sequence.

A novel secretory pathway for interleukin-1 beta, a protein lacking a signal sequence.

Potassium-inhibited processing of IL-1 beta in human monocytes.

Incorporation of Bovine Herpesvirus 1 Protein Subunits into Large Unilamellar and Multilamellar Liposomes

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