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Infection and Immunity, May 2000, p. 2925-2929, Vol. 68, No. 5
Department of Internal
Medicine,1 Department of
Pathology,3 and Department of
Biochemistry,4 Institute of Tropical
Medicine, and First Department of Internal Medicine, School of
Medicine,7 Nagasaki University, Nagasaki,
Department of Metabolic Disease, Nijigaoka Hospital,
Nagasaki,2 Department of Molecular
Oncology, Cancer Research Institute, Kanazawa University School of
Medicine, Kanazawa,5 and Department
of Molecular Preventive Medicine, School of Medicine, The
University of Tokyo, Tokyo,6 Japan
Received 22 November 1999/Returned for modification 17 January
2000/Accepted 7 February 2000
To elucidate the mechanism of the high incidence of lower
respiratory tract infections in patients with diabetes mellitus, we
investigated the kinetics of production of macrophage inflammatory protein 2 (MIP-2), an important mediator of lung neutrophil
recruitment, using mice with streptozotocin-induced diabetes.
Intratracheal challenge with 1 mg of lipopolysaccharide (LPS), an
endotoxin, per kg of body weight resulted in a time-dependent increase
in the levels of MIP-2 protein in bronchoalveolar lavage (BAL) fluid, with the peak concentration (49.4 ± 13 ng/ml) occurring at 3 h and significant neutrophil accumulation becoming apparent by 3 h
in normal mice. In diabetic mice, the peak level of MIP-2 protein in
BAL fluid did not occur until 6 h and was reduced to 21.9 ± 10 ng/ml. Immunohistochemical studies using anti-MIP-2 antibody confirmed that the main cellular source of MIP-2 in the lung after LPS
challenge was alveolar macrophages (AMs) in normal mice. The lungs in
diabetic mice, however, showed no AMs staining for MIP-2 within 3 h after LPS challenge. PCR analysis using whole-lung RNA showed a
time-dependent increase in MIP-2 mRNA levels after LPS instillation.
The level of MIP-2 mRNA in diabetic mice was markedly decreased
compared to that in normal mice. Our results indicate that impairment
of MIP-2 mRNA expression in the AMs in diabetic mice resulted in
delayed neutrophil recruitment in the lungs, and this may explain the
development and progression of pulmonary infection in diabetes mellitus.
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Impairment of Endotoxin-Induced Macrophage
Inflammatory Protein 2 Gene Expression in Alveolar Macrophages in
Streptozotocin-Induced Diabetes in Mice
*
Corresponding author. Mailing address: Department of
Internal Medicine, Institute of Tropical Medicine, Nagasaki University, 1-12-4 Sakamoto, Nagasaki City, Nagasaki 852-8523, Japan. Phone: 81-95-849-7841. Fax: 81-95-849-7843. E-mail:
chinu{at}ceres.dti.ne.jp.
Infection and Immunity, May 2000, p. 2925-2929, Vol. 68, No. 5
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
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