Role of macrophages in the pathogenesis of encephalomyocarditis virus-induced diabetes in mice.
Pancreatic islets from SJL/J mice infected with the D variant of encephalomyocarditis virus (EMC-D virus) showed lymphocytic infiltration with moderate to severe destruction of beta cells. Immunohistochemical staining of the islet sections with several monoclonal antibodies, anti-Mac-1, anti-Mac-2, and F4/80 for macrophages, anti-L3T4 for helper/inducer T cells, and anti-Lyt2 for cytotoxic/suppressor T cells revealed that the major population of infiltrating cells at the early stage of viral infection was Mac-2-positive macrophages. In contrast, macrophages detected by anti-Mac-1 and F4/80 monoclonal antibodies were not found at the early stage of viral infection but were found at intermediate and late stages of viral infection. Helper/inducer T cells and cytotoxic/suppressor T cells also infiltrated the islets at intermediate and late stages of viral infection. Short-term treatment of mice with silica prior to viral infection resulted in an enhancement of beta-cell destruction, leading to the development of diabetes. In contrast, long-term treatment of mice with silica resulted in complete prevention of diabetes caused by a low dose of viral infection and a significant decrease in the incidence of diabetes caused by an intermediate or high dose of viral infection. Furthermore, depletion of macrophages by a specific monoclonal antibody (anti-Mac-2) resulted in a much greater decrease in the incidence of diabetes caused by an intermediate dose of viral infection. However, suppression of helper/inducer T cells and cytotoxic/suppressor T cells, by anti-L3T4 and anti-Lyt2 antibodies, respectively, did not alter the incidence of diabetes. On the basis of these data, it is concluded that macrophages, particularly Mac-2-positive macrophages, play a crucial role in the process of pancreatic beta-cell destruction at the early stage of encephalomyocarditis D virus infection in SJL/J mice.
Baek
H S
HS
Department of Microbiology and Infectious Diseases, Faculty of Medicine, University of Calgary, Alberta, Canada.
Yoon
J W
JW
D000818:Animals; D000911:Antibodies, Monoclonal; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology / Q000517:prevention & control; D004686:Encephalomyocarditis virus / Q000472:pathogenicity*; D006029:Glycosuria; D007515:Islets of Langerhans / Q000473:pathology; D007657:Ketone Bodies / Q000652:urine; D008264:Macrophages / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009336:Necrosis; D012822:Silicon Dioxide / Q000627:therapeutic use
D000911:Antibodies, Monoclonal; D001786:Blood Glucose; D007657:Ketone Bodies; D012822:Silicon Dioxide