There are increasing clinical (1-6), functional (7), radiological (4,5,6,8), and histological (3,(9)(10)(11)(12)(13)(14) evidences that interstitial pneumonitis with or without pulmonary fibrosis may develop in patients with underlying diseases which appear to be associated with circulating antigen-antibody complexes. The pathogenesis of these human lesions, however, has not been studied in experimental animal models. Rabbits with acute or chronic serum sickness have not shown pulmonary changes (15, 16). On the other hand, acute anaphylactic shock, a condition characterized by preferential precipitation of circulating antigen-antibody complexes within the lumina of pulmonary capillaries (17)(18)(19), is caused by a mechanism which has no relationship with chronic pulmonary diseases in man.These considerations have suggested the possibility that antigen-antibody complexes present in large amount and for prolonged periods of time in the circulation of rabbits may localize in their lungs, thereby producing inflammatory reactions comparable to those commonly seen in the kidneys of the same animals.The results of the studies described here show that rabbits making a hyperactive antibody response to injections of bovine serum albumin (BSA), 1 when maintained in a state of relative antigen-antibody equivalence by high, multiple, daily doses of BSA, develop membranous and/or proliferative lesions of the lung which are associated with deposition of antigen, host immunoglobulin, complement, and fibrinogen in pulmonary structures. The inflammatory changes, which are presumably produced by antigen-antibody complexes, cover the morphologic spectrum of certain human interstitial pneumonitis (20, 21). Materials and MethodsInduction of Serum Sickness.--58 female albino rabbits weighing 2-3 kg were purchased from a local breeder, and fed Purina rabbit pellets and water ad libitum. 51 rabbits were used

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The mechanisms that allow circulating basement membrane antibodies (Ab) to interact with the alveolar basement membrane (ABM) inducing Goodpasture's hemorrhagic pneumonitis are unknown. In laboratory animals the ABM is inaccessible to phlogogenic amounts of ABM Ab unless the permeability of the unfenestrated alveolar endothelium is increased. This study was designed to test the hypothesis that in the mouse polypeptide mediators, generated by activated lymphoid cells or cells infected by viruses, contribute to the pathogenesis of passive Goodpasture's hemorrhagic pneumonitis. In naive mice that received rabbit ABM Ab, these bound to the glomerular basement membrane but not to the ABM and their lungs were normal. In the lungs of mice injected with human recombinant IL-2 and IFN-a specific binding of ABM IgG, C3, and fibrinogen to the ABM, diffuse and severe erythrocyte extravasation, and accumulation of mononuclear and polymorphonuclear leukocytes were constantly observed. ABM Ab and IL-2 or ABM Ab and IFN-a did not produce comparable effects. Mice injected only with IL-2 and IFN-a had enlarged, edematous lungs without pulmonary hemorrhages. The results show that the synergism of IL-2 and IFN-a convert the lung into a preferential target for AMB Ab, suggesting that cytokines may have a role in the pathogenesis of human Goodpasture's pneumonitis. (J. Clin. Invest. 1990Invest. . 85:1507Invest. -1515 Goodpasture's pneumonitis * basement membrane antibodies.

The possible role of circulating immune complexes (IC) in the production gastrointestinal lesions was studied in rabbits with chronic serum sickness (CSS) induced by multiple daily injections of bovine serum albumin (BSA). All rabbits generating a marked antibody response developed IC glomerulonephritis. In approximately 50% of these rabbits granular deposits of BSA, rabbit IgG, and C3 were also found in the gastrointestinal tract. The immune deposits in the gastrointestinal tract were mainly present in the vessel walls, close to the intestinal glands and the surface epithelium, and between the smooth muscle cells. This was accompanied by slight to moderate edema of the mucosa and the submucosa and mild infiltration of inflammatory cells. Electron-densedeposits were found in a pattern corresponding to that observed for BSA, rabbit IgG, and C3. Degranulated neutrophils, basophils, and mast cells were noticed in the interstitium. The presence in the same areas of granular deposits of BSA, IgG, and C3, corresponding to electron-dense deposits, suggests that the deposits contain BSA-anti-BSA complexes. These findings show that in rabbits with CSS circulating IC may localize and induce injury in the gastrointestinal tract.

This paper describes the release of platelet-activating factor (PAF) into the circulation of rabbits with acute pulmonary injury induced by antibody reacting with pulmonary endothelium. Eight rabbits were injected i.v. with 2 mg/kg of body weight of goat anti-rabbit lung angiotensin-converting enzyme gamma-globulin (GtARbACE). All animals developed acute pneumonitis, characterized by severe endothelial damage, accumulation of polymorphonuclear leukocytes (PMN) and platelets (Plt) in the lumina of alveolar capillaries, and deposits of goat IgG and rabbit C3 along alveolar capillary walls. Six of the rabbits died from acute pulmonary edema. PAF was detected in the plasma of all animals within 5 min after injection of GtARbACE. Five other rabbits were depleted of leukocytes by nitrogen mustard and then injected with 2 mg/kg of body weight of GtARbACE. In three of these rabbits release of PAF was demonstrated, though in amounts smaller than in non-leukocyte-depleted rabbits; all three animals died from pulmonary edema. After injection of 0.03 mg/kg of body weight of GtARbACE in six additional rabbits, three of them leukocyte-depleted, small amounts of PAF were detected in the circulation. None of these six rabbits died of pulmonary edema. PAF release was not observed in ten rabbits injected i.v. with 2 or 0.03 mg/kg of body weight of normal goat gamma-globulin. In separate experiments in vitro, incubation of isolated lung or thoracic aorta with GtARbACE resulted in deposits of goat IgG along endothelia and significant release of PAF. PAF was also released from endothelial cells removed from thoracic aorta by cellulose acetate paper and then incubated with GtARbACE. When segments of thoracic aorta were stripped of endothelium and then incubated with GtARbACE, PAF release could not be shown. The data obtained are consistent with the interpretation that PAF released into the circulation after binding of GtARbACE to the endothelia of lung and aorta originates from leukocytes and from lung and thoracic aorta endothelial cells.

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Cytomegalovirus (CMV) infection continues to be a major cause of morbidity and mortality in transplant recipients, yet prompt diagnosis remains a problem. A new assay has been developed that detects CMV antigens in peripheral blood leukocytes (CMV-AG). A retrospective analysis of the experience with this assay was performed, and its usefulness in the diagnosis of CMV infection in renal transplant recipients with unexplained fever was compared with that of conventional modalities (buffy coat culture, detection of circulating anti-CMV immunoglobulin M). The results suggest that the CMV-AG assay is a more rapid and sensitive test than existing modalities in the early diagnosis of CMV infection. When expressed quantitatively, it can discriminate between CMV infection and CMV disease, and it is useful in monitoring the course of infection and the response to therapy.