Diabetes-induced alteration of F4/80+ macrophages: a study in mice with streptozotocin-induced diabetes for a long term
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Macrophages as an early stage of immune responses form a bridge between innate and acquired immunity and shape the adaptive immune response. The immunoregulatory functions of macrophages in hosts with a prolonged exposure to a diabetic milieu remain to be determined. The levels, phenotype, and immunity including antigen-presenting ability, phagocytosis and immunogenicity of F4/80+ splenic macrophages (SPMs), and peritoneal exudates macrophages (PEMs) were detected in age-matched control mice and mice with streptozotocin (STZ)-induced diabetes for 16 weeks. The numbers of F4/80+ SPMs and PEMs significantly decreased in STZ-induced diabetic mice, compared with age-matched non-diabetic mice (control) at 16 weeks after diabetes induction. Functional analysis showed that F4/80+ SPMs and PEMs in STZ-induced diabetic mice exhibit significantly lower immunogenicity and nonopsonic phagocytosis to allogeneic T cells than those of control mice both in vitro and in vivo. Coincidently, the antigen-presenting capacity of F4/80+ PEMs, but not F4/80+ SPMs, in mice with STZ-induced diabetes for 16 or more weeks is also significantly lower than that of control mice. Our results showed that total cell number and immune function of F4/80+ macrophages were significantly defective in mice with a prolonged exposure to a diabetic milieu, which may be a mechanism responsible for the increased macrophage-related complications in diabetic patients such as the high prevalence of infection and cardiovascular mortality.
KeywordsMonocytes/macrophages Diabetes Autoimmune Immunodeficiency Diabetic complications
median fluorescence intensity
mixed leukocyte reactions
peritoneal exudate macrophages
The authors wish to thank Dr. Hong Shen for her kind review of the manuscript; Ms. Jing Wang, Mr. Yabing Liu, and Ms. Jianxia Peng for their expert technical assistance; Ms. Qinghuan Li for her excellent laboratory management; and Ms. Yuli Liu for her outstanding animal husbandry. This work was supported by grants from the National Natural Science Foundation for Key Programs (C30630060, Y.Z.), the National Natural Science Foundation for Young Scientists (C30600567, G.L.), the National Natural Science Foundation for Distinguished Young Scholars (C03020504, Y.Z.), and the Scientific Research Foundation for Returned Overseas Chinese Scholars, State Education Ministry (2005-546, Y.Z.).
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