| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1 From the Laboratory for Surgical Research, Children’s Hospital, Boston, Massachusetts; 2 Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts; 3 Department of Ophthalmology and Visual Science, Kyoto University Graduate School of Medicine, Kyoto, Japan; 4 Vascular Research Division, Departments of Pathology, Harvard Medical School, Brigham and Women’s Hospital, Boston, Massachusetts; 5 Department of Ophthalmology, Harvard Medical School, Joslin Diabetes Center, Boston, Massachusetts.
PURPOSE. A critical early event in the pathogenesis of diabetic retinopathy is leukocyte adhesion to the diabetic retinal vasculature. The process is mediated, in part, by intercellular adhesion molecule-1 (ICAM-1) and results in blood–retinal barrier breakdown and capillary nonperfusion. This study evaluated the expression and function of the corresponding ICAM-1–binding leukocyte ß2-integrins in experimental diabetes.
METHODS. Diabetes was induced in Long Evans rats with streptozotocin. The expression of the surface integrin subunits CD11a, CD11b, and CD18 on rat neutrophils isolated from peripheral blood was quantitated with flow cytometry. In vitro neutrophil adhesion was studied using quantitative endothelial cell–neutrophil adhesion assays. The adhesive role of the integrin subunits CD11a, CD11b, and CD18 was tested using specific neutralizing monoclonal antibodies. CD18 bioactivity was blocked in vivo with anti-CD18 F(ab')2 fragments, and the effect on retinal leukocyte adhesion was quantitated with acridine orange leukocyte fluorography.
RESULTS. Neutrophil CD11a, CD11b, and CD18 surface integrin levels were 62% (n = 5, P = 0.006), 54% (n = 5, P = 0.045), and 38% (n = 5, P = 0.009) greater in diabetic versus nondiabetic animals, respectively. Seventy-five percent more neutrophils from diabetic versus nondiabetic animals adhered to rat endothelial cell monolayers (n = 6, P = 0.02). Pretreatment of leukocytes with either anti-CD11b or anti-CD18 antibodies lowered the proportion of adherent diabetic neutrophils by 41% (n = 6, P = 0.01 for each treatment), whereas anti-CD11a antibodies had no significant effect (n = 6, P = 0.5). In vivo, systemic administration of anti-CD18 F(ab')2 fragments decreased diabetic retinal leukostasis by 62% (n = 5, P = 0.001).
CONCLUSIONS. Neutrophils from diabetic animals exhibit higher levels of surface integrin expression and integrin-mediated adhesion. In vivo, CD18 blockade significantly decreases leukostasis in the diabetic retinal microvasculature. Integrin adhesion molecules may serve as therapeutic targets for the treatment and/or prevention of early diabetic retinopathy.
This article has been cited by other articles:
|
|
 |
|
  D. Skondra, K. Noda, L. Almulki, F. Tayyari, S. Frimmel, T. Nakazawa, I. K. Kim, S. Zandi, K. L. Thomas, J. W. Miller, et al. Characterization of Azurocidin as a Permeability Factor in the Retina: Involvement in VEGF-Induced and Early Diabetic Blood-Retinal Barrier Breakdown Invest. Ophthalmol. Vis. Sci., February 1, 2008; 49(2): 726 - 731. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-J. You, C.-H. Yang, J.-S. Huang, M.-S. Chen, and C.-M. Yang Fractalkine, a CX3C Chemokine, as a Mediator of Ocular Angiogenesis Invest. Ophthalmol. Vis. Sci., November 1, 2007; 48(11): 5290 - 5298. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Chen, A. M. Guo, P. A. Edwards, G. Trick, and A. G. Scicli Role of NADPH oxidase and ANG II in diabetes-induced retinal leukostasis Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2007; 293(4): R1619 - R1629. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. McLeod A chronic grey matter penumbra, lateral microvascular intussusception and venous peduncular avulsion underlie diabetic vitreous haemorrhage Br. J. Ophthalmol., May 1, 2007; 91(5): 677 - 689. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Hafezi-Moghadam, K. Noda, L. Almulki, E. F. Iliaki, V. Poulaki, K. L. Thomas, T. Nakazawa, T. Hisatomi, J. W. Miller, and E. S. Gragoudas VLA-4 blockade suppresses endotoxin-induced uveitis: in vivo evidence for functional integrin up-regulation FASEB J, February 1, 2007; 21(2): 464 - 474. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. K.H. Cheung, M. K.L. Fung, A. C.Y. Lo, T. T.L. Lam, K. F. So, S. S.M. Chung, and S. K. Chung Aldose Reductase Deficiency Prevents Diabetes-Induced Blood-Retinal Barrier Breakdown, Apoptosis, and Glial Reactivation in the Retina of db/db Mice Diabetes, November 1, 2005; 54(11): 3119 - 3125. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Y. Kim, M. A. Johnson, D. S. McLeod, T. Alexander, B. C. Hansen, and G. A. Lutty Neutrophils Are Associated With Capillary Closure in Spontaneously Diabetic Monkey Retinas Diabetes, May 1, 2005; 54(5): 1534 - 1542. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. K. Krady, A. Basu, C. M. Allen, Y. Xu, K. F. LaNoue, T. W. Gardner, and S. W. Levison Minocycline Reduces Proinflammatory Cytokine Expression, Microglial Activation, and Caspase-3 Activation in a Rodent Model of Diabetic Retinopathy Diabetes, May 1, 2005; 54(5): 1559 - 1565. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. X. Zhang, J.-x. Ma, J. Sima, Y. Chen, M. S. Hu, A. Ottlecz, and G. N. Lambrou Genetic Difference in Susceptibility to the Blood-Retina Barrier Breakdown in Diabetes and Oxygen-Induced Retinopathy Am. J. Pathol., January 1, 2005; 166(1): 313 - 321. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J R MacKinnon, R M Knott, and J V Forrester Altered L-selectin expression in lymphocytes and increased adhesion to endothelium in patients with diabetic retinopathy Br. J. Ophthalmol., September 1, 2004; 88(9): 1137 - 1141. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. C. Mamputu and G. Renier Advanced glycation end-products increase monocyte adhesion to retinal endothelial cells through vascular endothelial growth factor-induced ICAM-1 expression: inhibitory effect of antioxidants J. Leukoc. Biol., June 1, 2004; 75(6): 1062 - 1069. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Canton, E. M. Martinez-Caceres, C. Hernandez, C. Espejo, J. Garcia-Arumi, and R. Simo CD4-CD8 and CD28 Expression in T Cells Infiltrating the Vitreous Fluid in Patients With Proliferative Diabetic Retinopathy: A Flow Cytometric Analysis Arch Ophthalmol, May 1, 2004; 122(5): 743 - 749. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Miyahara, J. Kiryu, K. Yamashiro, K. Miyamoto, F. Hirose, H. Tamura, H. Katsuta, K. Nishijima, A. Tsujikawa, and Y. Honda Simvastatin Inhibits Leukocyte Accumulation and Vascular Permeability in the Retinas of Rats with Streptozotocin-Induced Diabetes Am. J. Pathol., May 1, 2004; 164(5): 1697 - 1706. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M R Stanford The pathogenesis of diabetic retinopathy Br. J. Ophthalmol., April 1, 2004; 88(4): 444 - 445. [Full Text] [PDF]
|
|
|
|
|
|
J M Hughes, A Brink, A N Witmer, M Hanraads-de Riemer, I Klaassen, and R O Schlingemann Vascular leucocyte adhesion molecules unaltered in the human retina in diabetes Br. J. Ophthalmol., April 1, 2004; 88(4): 566 - 572. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R Donnelly, I Idris, and J V Forrester Protein kinase C inhibition and diabetic retinopathy: a shot in the dark at translational research Br. J. Ophthalmol., January 1, 2004; 88(1): 145 - 151. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Dandona, A. Aljada, P. Mohanty, H. Ghanim, A. Bandyopadhyay, and A. Chaudhuri Insulin Suppresses Plasma Concentration of Vascular Endothelial Growth Factor and Matrix Metalloproteinase-9 Diabetes Care, December 1, 2003; 26(12): 3310 - 3314. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. C. B. Moore, J. E. Moore, Y. Kaji, N. Frizzell, T. Usui, V. Poulaki, I. L. Campbell, A. W. Stitt, T. A. Gardiner, D. B. Archer, et al. The Role of Advanced Glycation End Products in Retinal Microvascular Leukostasis Invest. Ophthalmol. Vis. Sci., October 1, 2003; 44(10): 4457 - 4464. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Sennlaub, F. Valamanesh, A. Vazquez-Tello, A.M. El-Asrar, D. Checchin, S. Brault, F. Gobeil, M.H. Beauchamp, B. Mwaikambo, Y. Courtois, et al. Cyclooxygenase-2 in Human and Experimental Ischemic Proliferative Retinopathy Circulation, July 15, 2003; 108(2): 198 - 204. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Chibber, B. M. Ben-Mahmud, G. E. Mann, J. J. Zhang, and E. M. Kohner Protein Kinase C {beta}2-Dependent Phosphorylation of Core 2 GlcNAc-T Promotes Leukocyte-Endothelial Cell Adhesion: A Mechanism Underlying Capillary Occlusion in Diabetic Retinopathy Diabetes, June 1, 2003; 52(6): 1519 - 1527. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. T. Rosenbaum Sugar Creates a Sticky Business: Round Up the Usual Suspects Am. J. Pathol., May 1, 2002; 160(5): 1547 - 1550. [Full Text] [PDF]
|
|
|
|
 |
|
 A. J. Rassias, A. L. Givan, C. A. S. Marrin, K. Whalen, J. Pahl, and M. P. Yeager Insulin Increases Neutrophil Count and Phagocytic Capacity After Cardiac Surgery Anesth. Analg., May 1, 2002; 94(5): 1113 - 1119. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A P Adamis Is diabetic retinopathy an inflammatory disease? Br. J. Ophthalmol., April 1, 2002; 86(4): 363 - 365. [Full Text] [PDF]
|
|
|
|
|
|
A. M. Joussen, V. Poulaki, W. Qin, B. Kirchhof, N. Mitsiades, S. J. Wiegand, J. Rudge, G. D. Yancopoulos, and A. P. Adamis Retinal Vascular Endothelial Growth Factor Induces Intercellular Adhesion Molecule-1 and Endothelial Nitric Oxide Synthase Expression and Initiates Early Diabetic Retinal Leukocyte Adhesion in Vivo Am. J. Pathol., February 1, 2002; 160(2): 501 - 509. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Joussen, S. Huang, V. Poulaki, K. Camphausen, W.-D. Beecken, B. Kirchhof, and A. P. Adamis In Vivo Retinal Gene Expression in Early Diabetes Invest. Ophthalmol. Vis. Sci., November 1, 2001; 42(12): 3047 - 3057. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Joussen, T. Murata, A. Tsujikawa, B. Kirchhof, S.-E. Bursell, and A. P. Adamis Leukocyte-Mediated Endothelial Cell Injury and Death in the Diabetic Retina Am. J. Pathol., January 1, 2001; 158(1): 147 - 152. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. G. Soriano, P. Pacher, J. Mabley, L. Liaudet, and C. Szabo Rapid Reversal of the Diabetic Endothelial Dysfunction by Pharmacological Inhibition of Poly(ADP-Ribose) Polymerase Circ. Res., October 12, 2001; 89(8): 684 - 691. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
