Anti-complementary amines are immunological adjuvants in mice

Klerx, J.P.A.M.; Oosterhout, Antoon J. M. van; Dijk, Hans van; Kouwenberg, E. A.; Willers, J. M. N.

doi:10.1016/0165-2478(85)90102-6

Cited by 8 publications

(5 citation statements)

References 29 publications

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“…As far as effects on full serum were concerned, complete checkerboard titrations rather than one-point determinations with a single serum dilution were used, since these gave more re producible results. Figures 1-3 confirm and extend the previous find ings [21] indicating that dextran sulphate is much more anticomplementary than heparin in the mouse AP assay. The ratio of effectiveness on a weight basis of 68:1 in the normal AP assay was even flattered since the mean MW of heparin was about 14,000 [15], i.e.…”

Section: Discussionsupporting

confidence: 80%

“…1/36 of that of the dextran sulphate preparation used. It is noteworthy that the anticomplementary ef fects of the two polyanions in the human AP assay did not differ to such an extent [21]: an effectiveness ratio on a normal weight basis of 2:1 was observed. The ef fects of different dextran sulphate preparations on the guinea-pig AP were shown to be a reflection of the degree of sulphate substitution and the MW [8].…”

Section: Discussionmentioning

confidence: 97%

“…The differential anticomplementary effects of dex tran sulphate and heparin in the mouse AP assay [21] were studied in detail. As far as effects on full serum were concerned, complete checkerboard titrations rather than one-point determinations with a single serum dilution were used, since these gave more re producible results.…”

Section: Discussionmentioning

confidence: 99%

“…The effects of polyanions with respect to alterna tive pathway (AP) and terminal route activation. however, were shown to be species-dependent [21], Heparin, for instance, was not anticomplementary in the mouse AP assay. This phenomenon was paralleled by an absence of adjuvant activity in the protective re sponse of mice towards a killed Listeria vaccine.…”

Section: Introductionmentioning

confidence: 99%

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Analytic Study of the Differential Anticomplementary Effects of Dextran Sulphate and Heparin in the Assay for the Mouse Alternative Pathway

Klerx¹,

Dijk²,

Maaden³

et al. 1985

Int Arch Allergy Immunol

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In a recent paper, a linkage between immunological adjuvant activity in mice and in vitro anticomplementary (alternative pathway assay) effects was described for different polyanions. This connection was found only if mouse serum was used as a complement (C) source. In order to investigate the possible role of C in adjuvant activity, the differential effects of polyanions on mouse C were studied in detail. For this study, substances with different activity were selected, namely dextran sulphate with strong C-regulatory and immunoadjuvant activities, and heparin, which was weakly anticomplementary and devoid of adjuvant effect. In general, studies of mouse C are complicated by the inavailability of isolation procedures for the C-components involved. This difficulty was circumvented by making use of C5-deficient serum and of the haemolytic activity of mouse membrane attack complexes formed in the fluid phase. With yeast cells as alternative pathway activators it was shown that the effect of heparin on this pathway was restricted to activation of the terminal route. In contrast, dextran sulphate also caused a functional decay of a yeast-bound alternative pathway C5-convertase and interfered with the haemolytic activity of fluid-phase membrane attack complexes as well. Further studies will be needed to decide whether these specific effects of dextran sulphate are related to the immunological adjuvant activity of the substance in mice.

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Section: Discussionsupporting

confidence: 80%

Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Analytic Study of the Differential Anticomplementary Effects of Dextran Sulphate and Heparin in the Assay for the Mouse Alternative Pathway

Klerx¹,

Dijk²,

Maaden³

et al. 1985

Int Arch Allergy Immunol

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“…For example the toxic amines: ammonia, ethyldiamine and methylamine if injected simultaneously with antigen induce en hanced DH to sheep red blood cells [24]. The authors speculate that local depletion of complement factors by these amines is responsible for the observed en hancement of DH.…”

Section: Discussionmentioning

confidence: 98%

Potentiation of the Cellular Immune Response by Adjuvants: A Limited Role for Adjuvant Induced Interferon

Kraaijeveld¹,

Kamphuis²,

Benaissa-Trouw³

et al. 1986

Int Arch Allergy Immunol

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Adjuvants differ in capacity to induce interferon (IFN). As a consequence IFN induction by adjuvants may influence their effectiveness in enhancement of delayed type hypersensitivity (DH) reactions. In this study, the lipophilic amine dimethyl dioctadecyl ammonium bromide (DDA), the synthetic double-stranded polynucleotide polyinosinic polycytidylic acid (poly I:C), liposomes and the polyols L 101 and L 121 were compared in BALB/c mice as inducers of IFN and also as adjuvants for DH to both lysozyme and inactivated Semliki Forest virus (SFV). The antigens were injected intracutaneously, alone or mixed with adjuvant. At day 6 after the immunization, DH was elicited and measured 24 h later as increase in footpad thickness. Negatively charged liposomes and polyol L 121 were unable to enhance DH to SFV and also lack the capacity to induce IFN. Polyol L 101 induced low levels of IFN and showed only slight adjuvanticity for DH to SFV. In contrast, DDA, a moderate IFN inducer, was shown to be a very effective adjuvant for induction of DH against both lysozyme and SFV. The excellent IFN inducer, poly I:C, at the tested dose range (0.03–3.0 mg/kg), displayed only a relatively weak adjuvant activity. But low doses of poly I:C (0.03 and 0.1 mg/kg) showed still adjuvanticity in contrast to equal doses of DDA. This might be related to sufficient induction of IFN by low doses of poly I:C but not by DDA. The discrepancy observed in the relation between IFN induction and a maximal DH induction suggests that IFN is not the only factor which enhances the effectiveness of adjuvants in induction of DH. Furthermore, various inbred mouse strains display considerable differences in DDA-induced enhancement of DH to both lysozyme and SFV, whereas no significant differences in DDA-induced IFN titers were detected. In conclusion, the capacity of an adjuvant to induce IFN is an important feature to achieve enhancement of DH reactions. The effectiveness of an adjuvant, however, is also determined by its other intrinsic properties and by factors determined by the host.

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