Altered L-selectin expression in lymphocytes and increased adhesion to endothelium in patients with diabetic retinopathy

Br J Ophthalmol. 2004 Sep;88(9):1137-41. doi: 10.1136/bjo.2003.040329.

Abstract

Aim: To investigate L-selectin expression and shedding in patients with and without retinopathy and to determine if any observed changes are reflected by a functional change in the adhesion of leucocytes to an endothelial monolayer.

Methods: Age matched diabetic patients (26 with retinopathy, 19 without retinopathy) were compared to 24 non-diabetic controls to determine L-selectin surface protein expression, L-selectin mRNA production, and serum L-selectin levels by flow cytometry, RT-PCR, and ELISA, respectively. An adhesion assay was used to determine the binding of lymphocytes from the respective test groups to a monolayer of human endothelial cells.

Results: Significantly reduced (p = 0.004) L-selectin expression was demonstrated on lymphocytes (CD3+) from patients with diabetes compared to controls, the lowest levels being found in those with diabetic retinopathy (p = 0.004). L-selectin mRNA levels (p = 0.007) were significantly higher in the retinopathy group than in the no retinopathy group. Serum L-selectin levels were significantly higher (p = 0.04) in those with retinopathy compared to controls. Lymphocyte adhesion relative to control (100%) was essentially unchanged (84.0% (SD 27.7%), p = 0.15) for diabetic patients with no retinopathy and was markedly increased (192% (37.6%)) for those with retinopathy (p = 0.0001).

Conclusion: Lymphocyte activation, reduced surface L-selectin, increased circulating L-selectin, and a corresponding increase in adhesion of patients' cells using an in vitro assay, is evident in people with diabetic retinopathy. This suggests a role for lymphocyte activation in the pathogenesis of diabetic retinopathy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD3 Complex / immunology
  • Cell Adhesion / physiology
  • Diabetic Retinopathy / immunology
  • Diabetic Retinopathy / metabolism
  • Diabetic Retinopathy / physiopathology*
  • Endothelium, Vascular
  • Female
  • Flow Cytometry / methods
  • Humans
  • L-Selectin / metabolism*
  • Lymphocytes / blood
  • Lymphocytes / metabolism*
  • Male
  • Membrane Proteins / metabolism
  • Middle Aged
  • Phenotype
  • RNA, Messenger / metabolism

Substances

  • CD3 Complex
  • Membrane Proteins
  • RNA, Messenger
  • L-Selectin