Diabetic state-modified macrophages in GK rat release platelet-derived growth factor-BB for tube formation of endothelial cells in rat aorta.
Cultured peritoneal macrophages (M phi) of GK rats, a non insulin-dependent diabetes mellitus model established from normal Wistar rats, increased the tube formation of aortic endothelial cells (EC). A polyclonal anti-platelet-derived growth factor (PDGF)-BB (0.21-3.3 micrograms/ml) inhibited (by 66.5 +/- 6.6%) the tube-forming activity of conditioned medium (CM) from M phi in diabetic GK rats, but not that in age-matched normal Wistar rats. A polyclonal anti-interleukin (IL)-1 alpha (0.16-0.33%) also inhibited (by 37.7 +/- 5.8%) the activity of diabetic M phi-CM, and its inhibitory effect was smaller than that of anti-PDGF-BB. A monoclonal anti-basic fibroblast growth factor (bFGF) (0.6-60 ng/ml) inhibited the activities of CM from both M phi, respectively. The tube-forming activity of the normal M phi-CM was increased by the serum isolated from the diabetic GK rat more than by that from the age-matched normal Wistar rat. The activity of normal M phi-CM was also increased by 16.7-50 mM glucose-exposed serum. These tube-forming activities of the CM of M phi stimulated by diabetic serum and by the high concentration of glucose-treated serum were completely inhibited by anti-PDGF-BB. In conclusion, PDGF-BB was selectively released from the diabetic state-modified M phi in the GK rat to increase tube formation, suggesting a key role in the cause of angiogenesis. The diabetic state-induced activation may depend on advanced glycosylation endproducts produced in the serum in the diabetic rat.
Kobayashi
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S
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Japan.
Kimura
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I
Kimura
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M
D000818:Animals; D000925:Anticoagulants / Q000819:agonists; D001013:Aorta, Thoracic / Q000473:pathology; D000077214:Becaplermin; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000187:drug effects*; D005947:Glucose / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000378:metabolism*; D008297:Male; D051379:Mice; D009389:Neovascularization, Pathologic / Q000209:etiology*; D010982:Platelet-Derived Growth Factor / Q000378:metabolism* / Q000502:physiology*; D020574:Proto-Oncogene Proteins c-sis; D051381:Rats; D017208:Rats, Wistar
D000925:Anticoagulants; D017077:Culture Media, Conditioned; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D000077214:Becaplermin; D005947:Glucose