The Role of Monocytes in Acute Serum Sickness Nephritis

Despite extensive study of the immunological events in acute serum sickness in rabbits (1-3), the mechanism of glomerular inflammation and injury seen in this model has remained obscure (3). It has generally been thought that the glomerular inflammation, like the vasculitis, results from the activation of humoral mediator systems by deposited immune complexes, but no such mediator system has been identified (3). Specifically, complement and neutrophils, important in the pathogenesis of the vasculitis of serum sickness (3), and in the glomerular lesions of antiglomerular basement membrane nephritis (2), are not critical in the pathogenesis of the glomerular lesions in this model (3), and neutrophil infiltration is not a consistent finding in the glomerulus. In addition, the source of cells responsible for glomerular hypercellularity has not been definitively established. It has usually been assumed that hypercellularity results from an increased division of intrinsic glomerular cells, recently shown to be present in this model (4). But other authors (5, 6) have asserted on morphological grounds that glomerular hypercellularity results principally from infiltration by blood monocytes. The possibility that glomerular hypercellularity results from infiltration by monocytes suggests that cellular, rather than humoral, inflammatory mechanisms might be responsible for glomerular inflammation and injury in this model. For this reason we have studied the relative contributions of intrinsic glomerular cell division and monocyte infiltration to glomerular hypercellularity, using cell kinetic techniques, electron microscopy, and enzyme histochemistry. Our results demonstrate that glomerular hypercellularity is, indeed, principally a result of monocyte infiltration.