Altered cytokine and nitric oxide secretion in vitro by macrophages from diabetic type II-like db/db mice.
Macrophage dysfunction is a likely mechanism underlying common diabetic complications such as increased susceptibility to infection, accelerated atherosclerosis, and disturbed wound healing. There are no available studies on the function of tissue macrophages in diabetes in humans. We have therefore studied peritoneal macrophages from diabetic type 2-like db/db mice. We found that the release of tumor necrosis factor-alpha and interleukin-1beta from lipopolysaccharide plus interferon-gamma-stimulated macrophages and vascular endothelial growth factor from both stimulated and nonstimulated macrophages was significantly reduced in diabetic animals compared with nondiabetic controls. Nitric oxide production from the stimulated db/db macrophages was significantly higher than that in the db/+ cultures, whereas there was no difference in their ability to generate reactive oxygen species. When studied both at light and electron microscopic levels, macrophages in diabetic animals had an altered morphological appearance compared with those of normal controls. We conclude that the function and morphology of the macrophages are disturbed in db/db mice and that this disturbance is related to the mechanisms underlying common inflammatory and degenerative manifestations in diabetes.
Zykova
S N
SN
Institute of Medical Biology, University of Tromsø, Norway. svetlana@fagmed.uit.no
Jenssen
T G
TG
Berdal
M
M
Olsen
R
R
Myklebust
R
R
Seljelid
R
R
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000276:immunology / Q000503:physiopathology*; D016228:Endothelial Growth Factors / Q000378:metabolism; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism; D007773:Lactates / Q000097:blood; D008070:Lipopolysaccharides / Q000494:pharmacology; D008222:Lymphokines / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009569:Nitric Oxide / Q000378:metabolism*; D012016:Reference Values; D016897:Respiratory Burst; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D001786:Blood Glucose; D016207:Cytokines; D016228:Endothelial Growth Factors; D007375:Interleukin-1; D007773:Lactates; D008070:Lipopolysaccharides; D008222:Lymphokines; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D009569:Nitric Oxide