Effects of immunological adjuvants on the mouse complement system. I. The inability of the polyanion heparin to act as an adjuvant is paralleled by inefficient alternative complement pathway inhibition

Klerx, J.P.A.M.; Dijk, Hans van; Damen, H.; Rademaker, P.M.; Willers, J. M. N.

doi:10.1016/0192-0561(83)90048-6

Cited by 14 publications

(7 citation statements)

References 20 publications

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“…Immunol.]. Both DDA and DXS have been suggested to inhibit various processes involved in antigen elimination by the reticuloendo thelial system [4,5,7,16,17]. The data presented here suggest that the modes of action of the other surfact ants tested are comparable with that of DDA but are distinct from that of DXS.…”

Section: Discussionsupporting

confidence: 60%

“…Combining the syn thetic adjuvants dimethyldioctadecylammonium bro mide (DDA) and dextran sulfate (DXS) resulted in a synergistically enhanced humoral response to sheep red blood cells (SRBC) [14], The synergy is considered to be the consequence of different but complementary mechanisms responsible for the immunostimulating activity of either component. The surfactant DDA and the polyanion DXS differ in physicochemical [14], biological [2,3,7,9,16,17,[20][21][22][24][25][26], and immunostimulating [12 and accompanying paper] properties, and therefore we expected distinct modes of action. Consequently, synergistic stimulatory ac tivities of adjuvants might be expected if the modes of action are distinct.…”

Section: Introductionmentioning

confidence: 99%

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Synergistic Effects of Synthetic Adjuvants on the Humoral Immune Response

Hilgers¹,

Snippe²,

Jansze³

et al. 1986

Int Arch Allergy Immunol

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The effect of combinations of adjuvants on the humoral immune response to sheep red blood cells (SRBC) as antigen was investigated. Adjuvants belonging to two categories differing in physicochemical properties were used: surfactants (N, N-dioctadecyl-N′, N′-bis-(2-hydroyethyl)propanediamine (CP-20,961), dimethyldioctadecylammonium bromide (DDA), neutrally charged liposomes, polyol (L 101 and L 121) and polyanions [dextran sulfate (DXS), liquoid and suramine]. All adjuvants but suramine augmented humoral responses to 2 × 10⁷ SRBC measured by the number of direct anti-SRBC plaque-forming cells (PFC) in the spleen. The response to 2 × 10⁶ SRBC was enhanced considerably by L 121 and DXS but hardly or not at all by the other adjuvants. Combinations of two adjuvants were made at distinct ratios (1:3, 2:2, and 3:1) and injected intraperitoneally with 2 × 10⁶ SRBC. Low responses (5 × 10³ PFC per spleen) were induced by combinations of liquoid or suramine with DDA or DXS, and by combinations of CP-20,961 liposomes, L 101 or L 121 with DDA. Combinations of the surfactants DDA, CP-20,961, liposomes, L 101 or L 121 with DXS evoked responses which were significantly higher than the sum of responses supported by the single adjuvants. Ratios of 1:3 or 2:2 (surfactant: DXS) resulted in the most effective combinations. The data obtained suggest that only adjuvants derived from two different physicochemical groups are able to act synergistically.

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Section: Discussionsupporting

confidence: 60%

Section: Introductionmentioning

confidence: 99%

Synergistic Effects of Synthetic Adjuvants on the Humoral Immune Response

Hilgers¹,

Snippe²,

Jansze³

et al. 1986

Int Arch Allergy Immunol

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“…monocytogenes is an activator of the mouse alternative complement (C) pathway (ACP) (15). The adjuvant activity of polyanions in the listeria model corresponds to their anticomplementary effects on the mouse ACP in vitro (5). These observations suggested that the interaction of polyanions with the C cascade would be involved in their adjuvant effect.…”

mentioning

confidence: 77%

“…1B). This can probably be ascribed to the strong anticomplementary activity of this substance in the ACP assay, as observed in vitro with mouse serum as the C source (5). This explanation is strengthened by the finding that the listeria-induced enhancement of peritoneal C levels was not antagonized by the other polyanion, heparin (Kabi AB, Stockholm, Sweden) ( Fig.…”

mentioning

confidence: 86%

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Increased local complement levels upon intraperitoneal injection of mice with Listeria monocytogenes and regulation by polyanions

Klerx¹,

Beukelman²,

Dijk³

et al. 1985

Infect Immun

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Alternative complement pathway activity in mouse peritoneal fluid was determined by a sensitive microtiter assay with rabbit erythrocytes as target cells and cobra venom factor as the inducer of bystander hemolysis. The intra-and interstrain variations in five mouse strains were 30% and, maximally, 64%, respectively. No activity was detected in genetically C5-deficient mice. In C5-sufficient mice, intraperitoneal injection of heat-inactivated Listeria monocytogenes resulted in a 250% increase in local complement activity within 30 min. This effect was reversed by simultaneous injection of dextran sulfate but not heparin. These results are discussed in relation to the ability of listeriae to activate the mouse alternative complement pathway in vitro and the effectiveness of dextran sulfate and the failure of heparin in functioning as an adjuvant in the induction of a protective response in mice by a heat-inactivated listeria vaccine.

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Complement inhibitory and anticoagulant activities of fractionated heparins

Hennink

Klerx

Dijk

et al. 1984

Thrombosis Research

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Almost monodisperse heparin fractions (Rw/%r < 1.1) were obtained by gel filtration of a commercial heparin. These fractions were assayed for anticoagulant activity (thrombin times and APTT), chromogenic anti-factor Xa activity, inhibitory activity for the human classical complement pathway, carboxyl group content and total sulfate content. Linear relationships were observed between the molecular weight of the heparin fractions and the anticoagulant activities as determined by thrombin time-and APTTassay and the classical complement pathway inhibitory activity.On the other hand a hyperbolic-like relationship was observed between the molecular weight of the heparin fractions and the chromogenic anti-factor Xa activity. The heparin fractions did not show significant differences with respect to the carboxyl group and total sulfate content. Low-and high affinity heparin fractions were obtained by affinity chromatography using immobilized AT III. High-and low-affinity fractions greatly differed not only with respect to their APTT activity, but also where their complement-inhibitory activities were concerned. The latter in contrast to literature data available. These differences could not be explained by the observed differences in molecular weight of high and low affinity heparin respectively.

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Effects of immunological adjuvants on the mouse complement system. I. The inability of the polyanion heparin to act as an adjuvant is paralleled by inefficient alternative complement pathway inhibition

Cited by 14 publications

References 20 publications

Synergistic Effects of Synthetic Adjuvants on the Humoral Immune Response

Synergistic Effects of Synthetic Adjuvants on the Humoral Immune Response

Increased local complement levels upon intraperitoneal injection of mice with Listeria monocytogenes and regulation by polyanions

Complement inhibitory and anticoagulant activities of fractionated heparins

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