Glomerular Inflammation: A Consequence of Sequential Challenge of the Rat Mesangium with Particulate Macromolecules

Abstract

Imposil pretreatment (50 mg/100 g bodyweight) of male Sprague-Dawley rate (100-150 g), 24-48 h before an albumin-coated latex challenge resulted 24 h later in markedly reduced mesangial endocytosis of latex, compared with control animals receiving latex-albumin alone. This reduced capacity to ingest latex was associated with increased glomerular infiltration by Ia+ macrophages and mesangial localisation if immunoglobulins and complement C3c. In sharp contrast, pretreatment with albumin-coated latex had little effect on the subsequent mesangial uptake of Imposil. In this reverse situation macrophage infiltration was minimal, immunoglobulin deposition was similar to that in untreated control animals, and C3c was not detectable. Similarly, extending the interval between Imposil pretreatment and albumin-coated latex challenge up to 144h resulted in only minor infiltration by Ia+ macrophages and immunoglobulin localisation without accompanying C3c deposition, even though mesangial latex uptake was still limited. These observations demonstrate the consequences of secondary challenge following mesangial impairment due to a predisposing insult. Glomerular inflammation was dependent upon the timing and nature of the sequential challenge. The results support the concept that mesangial impairment following an initial insult may be a major factor in the predisposition to some forms of human glomerular inflammation.