Laboratory Investigation

Kidney International (1984) 26, 830–837; doi:10.1038/ki.1984.225

Detection of terminal complement components in experimental immune glomerular injury

Stephen Adler1, Patricia J Baker1, Pamela Pritzl1 and William G Couser1

1The Division of Nephrology, Department of Medicine, University of Washington, Seattle, Washington

Correspondence: Dr W G Couser, Division of Nephrology, Box RM-11, University of Washington, Seattle, Washington 98195, USA

Received 22 February 1984; Revised 29 May 1984.

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Abstract

Detection of terminal complement components in experimental immune glomerular injury. Complement mediates glomerulonephritis by inflammatory cell-dependent and non-inflammatory cell-independent effects on glomerular permeability. The latter may involve terminal components of the complement system. We examined several models of immunologic renal injury in the rat by immunofluorescence (IF) for terminal complement components C5, C6, C7, and C8 in glomeruli using antisera to human C5-8, which cross-react with the analogous rat complement components. Rats with the heterologous and autologous phases of passive Heymann nephritis (PHN) had proteinuria and 1 to 2+ capillary wall deposits of heterologous or rat IgG, rat C3, and C5-8. Complement depletion with cobra venom factor (CVF) significantly decreased proteinuria in both models and prevented deposition of all complement components. Rats with active Heymann nephritis had similar deposits of rat IgG and C5-8. Rats with anti-GBM nephritis and aminonucleoside nephrosis had severe proteinuria which was not affected by CVF treatment and deposits of C5-8 were absent. The presence of terminal complement components in immune deposits in experimental glomerular disease correlates with a functional role for complement in mediating glomerular injury. These data support the hypothesis that the terminal complement pathway may be a major mediator of some types of immune glomerular injury.

Détection des constituants terminaux du complément au cours de lésions immunes glomérulaires expérimentales. Le complément est le médiateur d'une glomérulonéphrite par des effets inflammatoires cellule-dépendants, et non inflammatoires cellule-indépendants sur la perméabilité glomérulaire. Ces derniers pourraient mettre en jeu les constituants terminaux du système complémentaire. Nous avons examiné plusieurs modèles de lésions rénales immunologiques chez le rat par la immunofluorescence (IF) en ce qui concerne les constituants complémentaires terminaux C5, C6, C7, et C8 dans les glomérules en utilisant des antisérums contre C5-8 humain qui croisent avec les constituants complémentaires analogues du rat. Des rats dans les phases hétérologue et autologue d'une néphrite passive de Heymann (PHN) avaient une proléinurie et des dépôts sur les parois capillaires 1 à 2 + d'IgG hétérologue ou de rat, de C3 et de C5-8 de rat. Une déplétion complémentaire avec du facteur de venin de cobra (CVF) a diminué significativement la protéinurie dans les deux modèles et a prévenu le dépôt de tous les constituants complémentaires. Des rats atteints d'une nephrite active de Heymann avaient des dépôts identiques d'IgG et de C5-8 de rat. Des rats atteints de néphrite anti-GBM et de néphrose aux aminoglucosides avaient une protéinurie sévère non affectée par le traitement au CVF et les dépôts de C5-8 étaient absents. La présence des constituants terminaux de complément dans les dépôts immuns lors des glomérulopathies expérimentales est corrélée avec un rôle fonctionnel du complément dans la médiation des lésions glomérulaires. Ces données sont en faveur de l'hypothèse que la voie terminale du complément peut être un médiateur majeur de certains types de lésions glomérulaires immunes.

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