| Benzo(a)pyrene (BaP), an environmental pollutant, is an immunosuppressant at high doses, but can enhance the immune response at low doses. Studies were conducted to determine if BaP would exacerbate development of autoimmune disease in genetically prone NZB/WF1 mice. Female NZB/WF1 mice were dermally exposed for thirty days. BaP did not increase markers of autoimmunity including proteinuria, total serum IgG, anti-dinitrophenol and anti-double stranded deoxyribonucleic acid antibodies.; BaP exposure did cause a significant increase in spleen weight, but not spleen cell number, which had not been seen in non-autoimmune strains. Hematological evaluation revealed a significant decrease in erythrocytes, hematocrit and hemoglobin; and an increase in mean corpuscular volume (MCV) and red cell distribution width (RDW). Clinically, these increases can indicate autoimmune hemolytic anemia (AIHA), which the NZB parent strain spontaneously develops.; Further studies revealed that the anemia was not autoimmune-mediated, but the result of non-immune hemolysis. Antibodies on the surface of erythrocytes and other signs of AIHA could not be detected using Coombs' tests, immune-mediated hemolysis assays, flow cytometry and blood smears. However, signs of hemolytic anemia were present. NZB/WF1 mice had lower levels of glucose-6-phosphate dehydrogenase activity when compared to non-autoimmune mice, erythrocytes were osmotically fragile and bilirubin was present in the urine. Bone marrow production was decreased at the highest level of BaP exposure, but not at all levels at which anemia was observed.; The splenomegaly was found to be due to extramedullary hematopoiesis, and splenic null cell expansion and increases in splenic CFU-e production were observed. Histopathology and immunomicroscopy confirmed the presence of null cells and megakaryocytes in the red pulp, consistent with the induction of compensatory hematopoiesis.; Although exposure to BaP did not result in exacerbation of autoimmune disease in NZB/WF1 mice, it did produce anemia and splenomegaly, both of which are seen in the NZB. However, the anemia observed in BaP-treated mice was not autoimmune-mediated. Nonetheless, a genetic component still exists, in that anemia seen in NZB/WF1 mice may result from fragile red blood cells, inherited from the NZB parent, lysed due to oxidative stress produced by BaP. |
