Platelet Proinflammatory and Hemostatic Function Is Differentially Regulated in Cystic Fibrosis.

Introduction: Platelet function and mechanisms of platelet-leukocyte interactions have been investigated in several vascular und inflammatory disorders. In most studies, platelet activation and an increase of platelet-leukocyte-aggregates (PLA) could be observed. We investigated platelet function in clinically stable patients with cystic fibrosis (CF).

Methods: In addition to routine markers of inflammation (e. g. CRP, IgG, ESR) parameters of platelet function were measured in 54 clinically stable CF patients and 55 healthy controls (age range 3 to 41 years): The percentage of P-selectin (CD62P) and PAC-1 (activated integrin α_IIbβ₃) positive resting and activated platelets (in-vitro activation with the thrombin receptor activating peptide 6) and the number of PLA were determined by flow cytometry. The plasma markers of platelet activation soluble P-selectin (sCD62P) and soluble CD40 ligand (sCD40L) were measured by ELISA. Furthermore, 15 CF patients and 14 healthy controls were investigated to determine CD41a-expression (integrin α_IIbβ₃) on resting and activated platelets as well as leukocyte expression of P-selectin-glycoprotein ligand 1 (PSGL-1, receptor of CD62P) and integrin α_Mβ₂.

Results: Chronic inflammation leads to a decrease of PAC-1-binding to resting and activated platelets. The effects were stronger in patients with higher markers of inflammation. CD41a expression was reduced on in-vitro-activated CF platelets. In contrast, proinflammatory platelet functions remained unchanged (CD62P-expression on resting and activated platelets) or increased (sCD62P, sCD40L, PLA). Leukocyte integrin α_Mβ₂ expression was increased and PSGL-1 expression remained unchanged in CF.

Discussion: Platelet function in clinically stable patients with CF is differentially regulated: Chronic inflammation leads to an upregulation of platelet proinflammatory function. In the presence of several procoagulatory mechanisms in inflammation there is a compensatory loss of platelet hemostatic function, shown by the decreased activation and exocytosis of the platelet major integrin α_IIbβ₃.