Serum sickness is a generalized acute inflammatory disease resulting from the deposition of circulating antigen-antibody (Ag-Ab) complexes in vascular structures (i, 2). The lesions observed include a proliferative and necrotic arteritis, endocarditis, myocarditis, acute glomerulonephritis, pulmonary vasculitis, cutaneous rash, synovitis and splenic granulomas. The pathologic alterations are produced by the interaction of the localized Ag-Ab complexes with many host humoral and cellular factors (3). Since the pathologic changes occur only after circulating Ag-Ab complexes accumulate in vascular structures, it was deemed important to examine the mechanisms responsible for the initial deposition of the complexes.In previous experiments of these mechanisms performed in this and other laboratories, the deposition of circulating colloidal carbon (4) or immune complexes (5, 6) in vessel walls was brought about by increasing the permeability of small blood vessels. The large complex molecules were then deposited beneath the endothelium, along the basement membrane, suggesting that the complexes were entrapped along a filtering surface (5). In several species histamine (4, 6) and serotonin (5-HT) (4) were shown to cause the increase in permeability. In addition, overloading of the reticuloendothelial system with carbon has led to the deposition of the carbon in the intima of certain vascular structures (4).Another factor that might influence deposition of Ag-Ab complexes is the hydrodynamic force of blood, suggested by the observation in serum sickness that coronary lesions are found frequently at aortic valve outflow areas and at major branches, particnlarly at bifurcations (1). It has been shown that hypertension increases the inci-* This is Publication 187 from

The present studies suggest that polymorphonuclear leukocytes (PMN's) are essential for the development of cardiovascular lesions in serum sickness. In the absence of PMN's, necrotic vascular lesions were never seen and endothelial proliferation in arteries was inhibited. Zones of fibrinoid deposits did not occur. By contrast, at least two-thirds of the control animals exhibited endothelial proliferation, and half had necrosis of arterial walls, usually with fibrinoid deposits. In arterial lesions that involved the intima and media, the internal elastic lamina was disrupted. This was associated with accumulations of PMN's and was prevented when PMN's were depleted. The observations suggested that the elastic lamina acts as a barrier to the outward spread of inflammation in arteries and that it is an important substrate of PMN action. Although glomerulitis and proteinuria developed in PMN-depleted animals, no conclusions could be drawn concerning the pathogenic role of PMN's in renal lesions, since PMN depletion could not be effected before the onset of immune elimination without influencing the immune response itself. Host complement (ß1C-globulin) was localized along with the antigen and rabbit gamma globulin in glomeruli and arteries showing lesions. In the glomeruli these deposits formed a granular lining along the area of the basement membrane. In arteries the fluorescent amorphous particles were in the intima and media of inflamed vessels. The immune response to BSA and the incidence and severity of cardiovascular and renal lesions were enhanced by the intravenous administration of pooled rabbit antiserum to BSA given 18 hours before BSA antigen and by injecting endotoxin along with the BSA. These additions to the usual procedure of inducing serum sickness did not appear to change the quality of the disease. In normal rabbits, the peak incidence of cardiovascular lesions was early in immune elimination of antigen, at a time when levels of circulating complexes was maximal. Conversely, the severest renal injury was noted several days later, at the completion of immune elimination.

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