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• W2079893726 abstract "Capillary occlusion is an early event in the development of diabetic retinopathy, and white blood cells have recently been shown to be involved. We have shown previously that pentoxifylline improves deformability and decreases F-actin content of unstimulated polymorphonuclear leukocytes from normal human subjects. The purpose of this study was to determine if pentoxifylline would improve three properties of unstimulated polymorphonuclear leukocytes from diabetic cats. The measured parameters were mechanical (whole cell deformability), structural (F-actin content) and biochemical (rate of superoxide anion production). Chronic hyperglycemia was induced in three cats by partial pancreatectomy, and they were kept in poor glycemic control for at least 6 months prior to the study. Polymorphonuclear leukocytes were isolated and the entry time of individual passive cells was measured during aspiration into a 4-μm micropipette under constant suction pressure (− 15 cmH2O). Deformability was defined as the inverse of the entry time. F-actin content of passive cells was measured by NBD-phallacidin labeling followed by flow cytometry. The rate of superoxide anion production was measured spectrophotometrically by superoxide dismutase-inhibitable cytochrome c reduction. Following incubation for 15 min with 0·1, 1·0 and 10·0 mm pentoxifylline, the average entry time of passive polymorphonuclear leukocytes was reduced from control by 11 ± 5% (P = 0·045), 17 ± 6% (P = 0·007), and 36 ± 5% (P < 0·001), respectively. The F-actin content decreased by 0%, 4 ± 0·6% (P < 0·001), and 10 ± 3% (P < 0·001), respectively. Superoxide anion production by resting polymorphonuclear leukocytes was reduced from control by 10 ± 7·6% (P ·05, not significant), 74 ± 7·6% (P < 0·001), and 100% (P < 0·001), respectively. Improved polymorphonuclear leukocyte deformability in the presence of pentoxifylline correlated to some extent with the decrease in F-actin content, and may result from a disruption of cytoplasmic structures that rely on F-actin for their integrity. The promotion of the passive state by pentoxifylline was further evidenced by the inhibition of superoxide anion production. These three effects may combine to reduce the risk of intravascular injury by polymorphonuclear leukocytes. Although achievable plasma levels of pentoxifylline are less than the concentrations used in this study, therapy would result in continuous exposure of polymorphonuclear leukocytes to the drug and its metabolites, and may therefore have the potential to be clinically effective in prevention of capillary occulusion and diabetic retinopathy." @default.
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• W2079893726 date "1992-12-01" @default.
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• W2079893726 title "Pentexifylline modulates deformability, F-actin content, and superoxide anion production of polymorphonuclear leukocytes from diabetic cats" @default.
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• W2079893726 doi "https://doi.org/10.1016/0014-4835(92)90009-h" @default.
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