Deficiency of the Sixth Component of Complement in Rabbits With an Inherited Complement Defect

Rother, Klaus; Rother, U.; Müller‐Eberhard, Hans J.; Nilsson, Ulf

doi:10.1084/jem.124.4.773

Cited by 88 publications

(27 citation statements)

References 22 publications

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“…Sera totally deficient in the 4th and 6th components of complement by functional assay were obtained, respectively, from guinea pigs with a genetically controlled deficiency of C4 (7), and rabbits with a genetically controlled C6 deficiency (8,9 addition of 2.0 ml of ice-cold EDTA buffer to each tube. The degree of lysis was recorded spectrophotometrically at 412 nm, and the C8 titer was expressed as that dilution of serum that would yield one effective C8 site/cell as calculated from the Poisson distribution and the one-hit theory of complement action (13).…”

Section: Methodsmentioning

confidence: 99%

A New Complement-Mediated Cytolytic Mechanism—the C1-Bypass Activation Pathway

May

Frank

1973

Proc. Natl. Acad. Sci. U.S.A.

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A new cytolytic pathway is described whereby cells sensitized with cytotoxic antibody can be specifically iysed in the complete absence of intact, classical complement pathway function. Evaluation of this model with sera deficient in the 4th (C4), 2nd (C2), and 6th (C6) components of complement has revealed that this new Iytic mechanism, termed the Cl-bypass activation pathway, is initiated by the antibody-mediated activation of C1. Utilizing components of the previously described alternate complement pathway, this pathway bypasses C4 and C2 to activate the third to ninth components of complement (C3-9) with induction of membrane damage.Serum complement (C) is the principal humoral cytotoxic effector system within the body, and a principal mediator of the biological events of inflammation. Until recently, complement activity was thought to result from the sequential activation of a single series of effector proteins. That is, antigen-antibody complexes were shown to activate in turn the first three components of complement C1, C4, and C2, termed the early components, and activation of these early components led to activation of C3-9, the later components in the complement sequence. A few years ago work from several laboratories established the existence of an alternate pathway of complement activation that bypassed C1, C4, and C2 of the "classical" pathway to enter the complement sequence at the level of C3 (1-4).Previous studies from our laboratory have shown that the alternate pathway is very inefficient at mediating the lysis of both erythrocytes and nucleated cells sensitized with cytotoxic antibody (5). In this report, for the first time, a new cytolytic system is described whereby cells sensitized with cytotoxic antibody can be specifically lysed in the complete absence of intact classical pathway function. Examination of this model has disclosed the existence of a novel cytotoxic complement pathway that is initiated by the attachment of C1 to membrane-bound antibody. The formation of an antigen-antibody-Cl complex (EAC1) leads to activation of components of the bypass or alternate complement pathway, and these in turn activate C3 and the later components of the complement sequence. MATERIALS AND METHODSPreparation of Anti-Forssman Antiserum and Purification of IgG Immunoglobulin. Anti-Forssman antiserum was prepared in a New Zealand white rabbit by repeated intravenous injections of increasing quantities of boiled sheep erythrocyte stromata over a 2.5-week period (10). 2 Weeks after the last intravenous injection of antigen, the rabbit was injected in each footpad with 0.2 ml of an emulsion containing equal volumes of antigen and Freund's complete adjuvant. 2 Weeks later, the animal was bled and the serum was used as a source of IgG hemolytic antibody. The IgG fraction of this antiserum was purified by gel filtration on Sephadex G-200 followed by sucrose density ultracentrifugation as described (6). 0.1 ml of a 1:1280 dilution of this antiserum was sufficient to produce 50% hemolysis of 0.1 ml of ...

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Section: Methodsmentioning

confidence: 99%

A New Complement-Mediated Cytolytic Mechanism—the C1-Bypass Activation Pathway

May

Frank

1973

Proc. Natl. Acad. Sci. U.S.A.

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“…The mouse serum was obtained from B10D2 old line mice (Jackson Laboratories, Bar Harbor, Maine) genetically deficient in C5 (15). The rabbit serum was obtained from C6-deficient rabbits (16). Each batch of EAC' cells could be used over a period of 7 days.…”

Section: Erythrocyte-antibody Complementmentioning

confidence: 99%

Binding of Soluble Immune Complexes to Human Lymphoblastoid Cells

Theofilopoulos

Dixon

Bokisch

1974

The Journal of Experimental Medicine

120

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“…2). In this respect the inheritance of C6 deficiency in this family resembles that noted in C6-deficient rabbits (18,37). The unexpected finding of an apparently healthy individual in the control population with a half-normal level of C6 raises the possibility that C6 deficiency in man may be less rare than expected.…”

mentioning

confidence: 76%