A study of the sensitivity of erythrocytes to lysis by heterologous sera via the alternative complement pathway

Dijk, Hans van; Heezius, Eric C. J. M.; Kooten, Peter J. S. van; Rademaker, P.M.; Dam, R Van; Willers, J. M. N.

doi:10.1016/0165-2427(83)90007-7

Cited by 9 publications

(1 citation statement)

References 16 publications

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“…We suggest that homologous restriction is actually a rather patchy phenomenon, dependent upon multiple parameters, including the nature of the target cell, the pathway through which complement is being activated, the species source of the activating antibody, as well as the source of complement. In more recent studies, human erythrocytes optimally sensitized with a rabbit polyclonal anti‐serum to activate the classical pathway were readily lysed by rat, rabbit and guinea pig serum, but were lysed poorly or not at all when exposed to human, horse or mouse serum [24]. Similar examples of species selectivity can be seen for other targets, activating principles and complement sources.…”

Section: The Phenomenon Of ’'Homologous Restriction’’ Of Complement Lmentioning

confidence: 88%

‘‘Homologous restriction’’ in complement lysis: roles of membrane complement regulators

Morgan

Berg

Harris

2005

Xenotransplantation

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The complement system is a powerful bactericidal immune defence with the potential to damage self cells. Protection of self is provided by expression on cells of a battery of membrane regulators that inhibit activation of complement. Roles of complement in the rejection of transplanted organs have long been recognized, and are particularly relevant in xenotransplantation, where hyperacute rejection is complement-driven. Inhibiting complement was therefore considered early in the history of xenografting, and the use of membrane complement regulators to this end was proposed more than two decades ago. For each of the membrane regulators in humans, early studies implied a species-specificity of action, inhibiting human complement but not that from other species. The dogma of species-specificity dictated strategies for inhibiting complement in xenografts and drove the creation of donor transgenic pigs expressing human regulators. Here we critically evaluate the evidence for species-specificity in membrane complement regulators from humans and other animals. We challenge the dogma and show that there is considerable cross-species activity for each of the membrane regulators of complement. Acceptance of the fact that species selectivity is not a limitation will open new avenues for protection of the xenograft from complement damage.

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Section: The Phenomenon Of ’'Homologous Restriction’’ Of Complement Lmentioning

confidence: 88%

‘‘Homologous restriction’’ in complement lysis: roles of membrane complement regulators

Morgan

Berg

Harris

2005

Xenotransplantation

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Microassay for colorimetric estimation of complement activity in guinea pig, human and mouse serum

Klerx

Beukelman

Dijk

et al. 1983

Journal of Immunological Methods

191

100

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Study of the optimal reaction conditions for assay of the mouse alternative complement pathway

Dijk

Rademaker

Klerx

et al. 1985

Journal of Immunological Methods

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The optimal reaction conditions for hemolytic assay of alternative complement pathway activity in mouse serum were investigated. A microtiter system was used, in which a number of 7.5 x 106 rabbit erythrocytes per test well appeared to be optimal. Rabbit erythrocytes were superior as target cells over erythrocytes from a number of other animal species. The optimal conditions were as follows: an incubation temperature of 39°C, an ionic strength of about 200 mM, and a magnesium concentration of 2.5 mM. Incubation during 60 rain was not sufficient for an end-point titration. Addition of 1 mg of zymosan A per test well, however, enhanced and accelerated the hemolytic activity of mouse serum via the alternative pathway resulting in a maximum value after 45 min. This, most probably, proceeded by a mechanism involving the formation of a zymosan-C5-convertase and bystander lysis of the target cells. In contrast to the normal alternative pathway assay the zymosan-potentiated test did, most probably, not involve natural antibodies. Cobra venom factor was more efficient in enhancing the sensitivity of the assay for the mouse alternative complement pathway than zymosan. This makes this factor very useful for testing C-poor body fluids.

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A study of the sensitivity of erythrocytes to lysis by heterologous sera via the alternative complement pathway

Cited by 9 publications

References 16 publications

‘‘Homologous restriction’’ in complement lysis: roles of membrane complement regulators

‘‘Homologous restriction’’ in complement lysis: roles of membrane complement regulators

Microassay for colorimetric estimation of complement activity in guinea pig, human and mouse serum

Study of the optimal reaction conditions for assay of the mouse alternative complement pathway

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