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

Abstract

Summary. Background: Platelets and leukocytes may in¯u-ence 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¯ow cytometry. Platelet± leukocyte cross-talk was studied in hirudinized whole blood incubated at 37 8C with stirring. Results: Basal single platelet P-selectin and leukocyte CD11b expression were similar in DM patients and healthy subjects, whilst circulating platelet±leu-kocyte aggregates and plasma elastase levels were elevated in DM patients. The thromboxane A 2 analog U46619 (3 Â 10 À7 M) induced more marked increases of platelet P-selectin expression and platelet±leukocyte aggregation in DM patients than in healthy subjects. The leukocyte-speci®c agonist N-formylmethionyl-leucyl-phenylalanine (fMLP) (10 À7 M) induced more marked CD11b expression in DM patients with microangiopathy, compared with healthy subjects. Platelet±leukocyte cross-talk induced by U46619 (10 À6 M) showed no difference between DM patients and healthy subjects. fMLP (10 À6 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.

Systemic Evaluation of Platelet and Leukocyte Activation and Interaction in a Rat Model of Pulmonary Arterial Hypertension

“…Previous studies have reported increased PLA formation in various clinical situations such as diabetic microangiopathy [15,29], acute myocardial infarction [14] and Raynaud’s phenomenon [16]. PLAs have been shown to be a more sensitive marker of platelet activation than platelet P-selectin expression [14].…”

“…Platelet-leukocyte aggregates (PLAs) are one of the important manifestations of these interactions. An increase in PLAs, which has been detected in coronary artery disease [14], diabetes [15] and autoimmune inflammatory diseases [13], has been suggested to participate in the pathogenesis of these diseases. In a recent report, systemic sclerosis patients with pulmonary hypertension were found to have higher numbers of PLAs [16].…”

Aspirin in the prevention of cardiovascular events in patients with diabetes

“…fibrinogen binding) is augmented. [74,78,[82][83][84] Production of inflammatory cytokines, Figure 6. Mechanisms underlying increased clot formation in patients with diabetes.…”

Food Intake Enhances Thromboxane Receptor–Mediated Platelet Activation in Type 2 Diabetic Patients but Not in Healthy Subjects

“…iabetes is associated with platelet hyperactivity (1,2), increases in circulating activated platelets and platelet-leukocyte aggregates (PLAs), and platelet hyperreactivity to in vitro stimulation (2,3). Thromboxane-mediated platelet activation is of special interest since diabetes is associated with increased platelet-dependent thromboxane A 2 (TxA 2 ) production (2), and diabetic patients appear to benefit less from prevention with aspirin than nondiabetic patients (4,5).…”