Alterations in Stimulus-Induced Integrin Expression in Peripheral Blood Neutrophils of Patients With Diabetic Retinopathy

Abstract

AbstractAdhesion molecule expression on peripheral blood leukocytes from diabetic patients with severe retinopathy and age-matched control subjects was assessed. Expression of CDllb, CD18, and L-selectin was measured on granulocytes and lymphocytes in whole blood within 1 hour of blood collection. Adhesion molecule expression was determined at 4° C, 37° C, and after stimulation with one of the chemotactic peptides, N-formyl-methionyl-leucyl-phenylalanine or p-phorbol 12-myristate 13-acetate. There were no differences between diabetics and controls in CD11b expression in neutrophils at 4° C, 37° C, or after N-formyl-methionyl-leucylphenylalanine stimulation. However, during stimulation with p-phorbol 12-myristate 13-acetate, the increase in CD11b expression in neutrophils from patients with diabetes was significantly less than in controls. In neutrophils, there was no difference between the control and diabetic participants in CD18 expression at 4° C, but after warming the cells to 37° C, the expression was significantly higher in patients with diabetes. The difference became even more apparent after N-formyl-methionyl-leucyl-phenylalanine stimulation. The increase in CD18 expression after p-phorbol 12-myristate 13-acetate stimulation of neutrophils was similar in control and diabetic participants. There was no difference in L-selectin expression in neutrophils under any conditions. There was no difference in adhesion molecule expression on lymphocytes under similar conditions. In summary, these observations indicate that integrin expression of neutrophils from patients with diabetes and retinopathy is altered after stimulation with neutrophil- activating agents. The changes were integrin-, stimulus-, and cell-specific, which suggests that the signal transduction mechanisms may be altered in diabetic neutrophils. These alterations may be responsible for abnormal leukocyte/endothelial interactions and microvascular complications in diabetic retinopathy.