The functions of circulatory polymorphonuclear leukocytes in diabetic patients with and without diabetic triopathy

Ohmori, Masami; Harada, Kazuhiro; Kitoh, Yasuhiko; Nagasaka, Syou-ichiroh; Saito, Toshikazu; Fujimura, Akio

doi:10.1016/s0024-3205(00)00509-9

Cited by 18 publications

(12 citation statements)

References 24 publications

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“…It was shown that gliclazide reduced oxidized low-density lipoprotein (LDL)-induced monocyte adhesion to cultured endothelial cells as well as vascular cell-mediated LDL oxidation in vitro [16] and that gliclazide given to patients with Type II diabetes inhibits the increased adhesiveness of diabetic monocytes to cultured endothelial cells [17]. This radical-scavenging activity could be one of the mechanism of the inhibition of leukostasis observed in this study, because leukocytes in diabetic animals have been reported to be more activated [1,4] and produce more oxygen-derived free radicals [5,6], which induce vascular endothelial dysfunction [7,8,9]. Recent studies demonstrated the increased expression of adhesion molecules under diabetic conditions [2,7,10,26,35].…”

Section: Discussionmentioning

confidence: 65%

“…A number of previous reports have indicated the importance of leukocyte entrapment in the pathogenesis of diabetic retinopathy [1,2,3,4,5,6,7,8,9,10,11,12] making leukocyte entrapment a therapeutic target for the prevention of this serious complication of diabetes. To date, only in vitro or ex vivo studies have been done that showed the inhibitory effects of gliclazide, a sulphonylurea hypoglycaemic drug, on enhanced adhesion of leukocytes to endothelial cells in high glucose conditions [16,17,18].…”

Section: Discussionmentioning

confidence: 99%

“…Diabetic retinopathy is a leading cause of adult vision loss and blindness and early-stage, preventive strategies are important research areas. Leukocyte adhesion to the diabetic retinal vasculature is presumed to be the critical early event in the pathogenesis of diabetic retinopathy [1,2,3], resulting in a breakdown in the blood-retinal barrier and in capillary nonperfusion [1,4,5,6,7,8,9,10,11,12]. In a rat model of diabetic retinopathy, investigators demonstrated retinal capillary occlusion by neutrophils and monocytes in histologic sections and found that areas of endothelial cell damage, capillary loss, and leukocyte extravasation existed adjacent to the static leukocytes [1].…”

mentioning

confidence: 99%

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Effective and selective prevention of retinal leukostasis in streptozotocin-induced diabetic rats using gliclazide

Kinoshita¹,

Kakehashi²,

Inoda

et al. 2002

Diabetologia

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Aims/hypothesis. Early stage leukocyte entrapment in the retinal microcirculation (retinal leukostasis) is considered to be one of the important pathogenetic events in diabetic retinopathy. Gliclazide, a sulphonylurea, was reported to reduce leukocyte adhesion to endothelial cells in hyperglycaemia in vitro, thus suggesting possible selective efficacy of this sulphonylurea in preventing leukostasis in diabetic patients. This study evaluated the effectiveness and selectivity of gliclazide treatment on retinal leukostasis of diabetic rats in vivo. Methods. Streptozotocin (STZ) (65 mg/kg)-induced diabetic rats were divided into three groups (n = 8 each): an untreated diabetic group, a gliclazide-treated diabetic group, and a glibenclamide-treated diabetic group. Gliclazide or glibenclamide was administered orally during a 3-week period. Non-diabetic rats were used as a control (n = 8). Retinal leukostasis was quantitatively evaluated in vivo by acridine orange leukocyte fluorography using a scanning laser ophthalmoscope.Results. The number of leukocytes trapped in the area around the optic disc in the untreated diabetic group (36.9 ± 5.1 cells) increased significantly compared with the non-diabetic control group (21.9 ± 2.9 cells; p = 0.0007). The number of leukocytes trapped in the gliclazide-treated diabetic group (23.5 ± 4.0 cells) decreased significantly compared with untreated diabetic group (p = 0.0008). In contrast, no reduction of retinal leukostasis was found in the glibenclamide-treated diabetic group (37.8 ± 5.8 cells; p = 0.7923). Conclusion/interpretation. This suggests that gliclazide could directly improve abnormalities in the retinal microcirculation independent of blood glucose control and possibly have selective therapeutic benefits in preventing early, critical events in diabetic retinopathy compared with other sulphonylurea drugs. [Diabetologia (2002) 45:735-739] Keywords Gliclazide, sulphonylurea, diabetic retinopathy, retinal leukostasis, acridine orange leukocyte fluorography, scanning laser ophthalmoscope. Diabetic retinopathy is a leading cause of adult vision loss and blindness and early-stage, preventive strategies are important research areas. Leukocyte adhesion to the diabetic retinal vasculature is presumed to be the critical early event in the pathogenesis of diabetic retinopathy [1,2,3], resulting in a breakdown in the blood-retinal barrier and in capillary nonperfusion [1,4,5,6,7,8,9,10,11,12]. In a rat model of diabetic retinopathy, investigators demonstrated retinal capillary occlusion by neutrophils and monocytes in histologic sections and found that areas of endothelial cell damage, capillary loss, and leukocyte extravasation existed adjacent to the static leukocytes [1]. In another post mortem study of human subjects, increased numbers of neutrophils were observed in the choroid and retina of patients with diabetes [2].

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Section: Discussionmentioning

confidence: 65%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Effective and selective prevention of retinal leukostasis in streptozotocin-induced diabetic rats using gliclazide

Kinoshita¹,

Kakehashi²,

Inoda

et al. 2002

Diabetologia

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“…increased incidence of coronary artery restenosis [11,12] and an exaggerated inflammatory response to organ ischaemia-reperfusion injury [13,14,15,16]. Neutrophils also influence the pathogenesis of microvascular complications, in particular diabetic retinopathy [17,18].…”

mentioning

confidence: 99%

“…Both spontaneous neutrophil adherence and fMLP-induced aggregation of neutrophils are associated with the presence of diabetic complications and in particular overt proteinuria [16,18]. Recently, an association has been identified between neutrophil elastase content, the concentration of glycaemia and angiopathy in diabetes [19,20].…”

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confidence: 99%

Impaired neutrophil actin assembly causes persistent CD11b expression and reduced primary granule exocytosis in Type II diabetes

2002

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Aims/hypothesis. Neutrophil dysfunction has a role in the pathogenesis of complications in Type II (non-insulin-dependent) diabetes mellitus. Neutrophils adhere through expression of the β 2 integrin CD11b/CD18 which closely associates with the actin cytoskeleton. The aim of this study was to investigate the effect of actin polymerisation on CD11b expression and exocytosis of the primary granule marker CD69 in neutrophils from patients with Type II diabetes. Methods. Neutrophils were activated with fMLP or PMA, actin polymerisation was inhibited with cytochalasin D. Cells were stained for CD11b and CD69 expression and intracellular F-actin was measured with phalloidin-FITC. Cellular fluorescence was measured by flow cytometry. Actin content of Triton X-100 fractions of cells was measured by SDS-PAGE and Coomassie blue staining. Results. PMA caused an increase in neutrophil F-actin that was greater in control subjects than in patients with Type II diabetes (50.8% vs 33.4%, p<0.001) and correlated with actin integrated optical density (IOD) by p=0.01). Loss of CD11b from cell surfaces only occurred in neutrophils with high Factin. The proportion of cells losing CD11b was lower in patients than in control subjects (23.1% vs 37.5%, p<0.001) and lowest in patients with additional cardiovascular risk markers (20.1% vs 27.7%; p<0.05). Cytochalasin D prevented loss of CD11b (p<0.001). CD69 expression was reduced in patients with Type II diabetes (22.6% vs 36.4%, p<0.001) and correlated with F-actin content (r=0.78, p<0.0001). Conclusion/interpretation. In Type II diabetes impaired neutrophil actin polymerisation leads to persistent expression of CD11b and reduced exocytosis of primary granules and could contribute to the pathogenesis of diabetic complications. [Diabetologia (2002) 45:719-727]

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Cytokines in diabetic nephropathy

Sytwu

Lin

2012

Advances in Clinical Chemistry

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The functions of circulatory polymorphonuclear leukocytes in diabetic patients with and without diabetic triopathy

Cited by 18 publications

References 24 publications

Effective and selective prevention of retinal leukostasis in streptozotocin-induced diabetic rats using gliclazide

Effective and selective prevention of retinal leukostasis in streptozotocin-induced diabetic rats using gliclazide

Impaired neutrophil actin assembly causes persistent CD11b expression and reduced primary granule exocytosis in Type II diabetes

Cytokines in diabetic nephropathy

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