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

Summary. Background: Platelets and leukocytes may influence each others' function, i.e. platelet–leukocyte cross‐talk. Diabetes mellitus (DM) is associated with platelet and leukocyte dysfunction. Objective: To evaluate platelet–leukocyte cross‐talk, and if this might contribute to platelet and leukocyte dysfunction and microangiopathy in DM patients. Patients and methods: 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 °C with stirring. Results: 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 × 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. Conclusions: 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.