Direct involvement of macrophages in destruction of beta-cells leading to development of diabetes in virus-infected mice.
A single administration of complete Freund's adjuvant (CFA), type 1 carrageenan (Car), or silica 7, 2, and 2 days, respectively, before infection with a low dose (1 x 10(2) plaque-forming units/mouse) of encephalomyocarditis D (EMC-D) virus resulted in a significant increase in the incidence of diabetes in SJL/J mice (100%) compared with untreated EMC-D virus-infected mice (40%). Peritoneal macrophages were isolated from uninfected SJL/J mice, which had been treated once with silica, and transferred into SJL/J mice 2 days before low-dose EMC-D infection. Approximately 90% of the mice became diabetic, whereas 30% of mice that received virus alone became diabetic. The depletion of macrophages by treatment with the combined anti-Mac-1 and anti-Mac-2 monoclonal antibodies after a single administration of CFA, Car, or silica resulted in almost complete prevention of beta-cell destruction in EMC-D virus-infected mice. Furthermore, none of the mice in which macrophages were depleted by long-term treatment with silica and 10% of the mice treated with Car before virus infection became diabetic. On the basis of these observations, we conclude that macrophages are directly involved in the destruction of beta-cells, leading to the development of clinical diabetes in EMC-D virus-infected mice.
Baek
H S
HS
Laboratory of Viral and Immunopathogenesis of Diabetes, Julia McFarlane Diabetes Research Centre, University of Calgary, Alberta, Canada.
Yoon
J W
JW
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D002351:Carrageenan / Q000008:administration & dosage; D003921:Diabetes Mellitus, Experimental / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D004686:Encephalomyocarditis virus / Q000472:pathogenicity*; D005455:Fluorescent Antibody Technique; D005620:Freund's Adjuvant / Q000008:administration & dosage; D007328:Insulin / Q000032:analysis; D007330:Insulin Antibodies; D007515:Islets of Langerhans / Q000382:microbiology / Q000473:pathology*; D007739:L Cells; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology / Q000502:physiology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D012822:Silicon Dioxide / Q000008:administration & dosage
D000911:Antibodies, Monoclonal; D007328:Insulin; D007330:Insulin Antibodies; D012822:Silicon Dioxide; D002351:Carrageenan; D005620:Freund's Adjuvant