Enhanced leukocyte–platelet cross‐talk in Type 1 diabetes mellitus: relationship to microangiopathy

Abstract

Platelets and leukocytes may influence each others' function, i.e. platelet-leukocyte cross-talk. Diabetes mellitus (DM) is associated with platelet and leukocyte dysfunction. To evaluate platelet-leukocyte cross-talk, and if this might contribute to platelet and leukocyte dysfunction and microangiopathy in DM patients. We evaluated platelet and leukocyte function, and cross-talk between these cells in Type 1 DM patients without (n = 19) and with (n = 20) microangiopathy, and healthy subjects (n = 27), using whole blood flow cytometry. Platelet-leukocyte cross-talk was studied in hirudinized whole blood incubated at 37 degrees C with stirring. Basal single platelet P-selectin and leukocyte CD11b expression were similar in DM patients and healthy subjects, whilst circulating platelet-leukocyte aggregates and plasma elastase levels were elevated in DM patients. The thromboxane A2 analog U46619 (3 x 10(-7) m) induced more marked increases of platelet P-selectin expression and platelet-leukocyte aggregation in DM patients than in healthy subjects. The leukocyte-specific agonist N-formyl-methionyl-leucyl-phenylalanine (fMLP) (10(-7) m) induced more marked CD11b expression in DM patients with microangiopathy, compared with healthy subjects. Platelet-leukocyte cross-talk induced by U46619 (10(-6) m) showed no difference between DM patients and healthy subjects. fMLP (10(-6) m) evoked marked leukocyte activation, which subsequently caused mild platelet P-selectin expression. This leukocyte-platelet cross-talk was more pronounced in DM patients than in healthy subjects. Furthermore, enhanced leukocyte-platelet cross-talk was correlated to platelet hyperreactivity among DM patients with microangiopathy only. Type 1 DM is associated with platelet and leukocyte hyperactivity, and enhanced leukocyte-platelet cross-talk, which may contribute to platelet hyperactivity and the microvascular complications seen in Type 1 DM.