Pentoxifylline modulates deformability, F-actin content, and superoxide anion production of polymorphonuclear leukocytes from diabetic cats.
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-micron 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Sonkin
P L
PL
Department of Ophthalmology, Duke University, Durham, NC 27710.
Freedman
S F
SF
Needham
D
D
Rao
K M
KM
Hatchell
D L
DL
D000199:Actins / Q000378:metabolism; D000818:Animals; D000838:Anions / Q000378:metabolism; D002415:Cats; D003930:Diabetic Retinopathy / Q000378:metabolism*; D004195:Disease Models, Animal; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D010431:Pentoxifylline / Q000494:pharmacology*; D013481:Superoxides / Q000378:metabolism*
D000199:Actins; D000838:Anions; D013481:Superoxides; D010431:Pentoxifylline