Platelets an Inflammatory Force in Transplantation

Abstract

Platelet interactions with dendritic cells, T cells and B cells have been best studied in vasculitis andatherosclerosis, but similar mechanisms may contribute to acute and chronic vascular lesions in transplants. In acute inflammation, platelets adhere to vessels and release mediators that increase endothelial cell activation and leukocyte recruitment. Adherent platelets can also augment antibody and cellular immune responses. Activated platelets recruit T cells and initiate a feedback loop. In this loop, platelets secrete chemokines to recruit T cells, and then activated T cells stimulate platelets through CD40-CD154 interactions to secrete more chemokines thereby recruiting more T cells. The interaction of platelets and T cells is enhanced by P-selectin/PSGL-1 stimulation. Both helper and cytotoxic T cells are stimulated by platelets. Antibody production that is stimulated through increased helper T-cell function can activate complement. This sets up another activation loop because platelets express receptors for antibodies and complement. In addition to inflammation, platelets stimulate repair by releasing growth factors and chemokines to recruit circulating vascular progenitor cells. These repair mechanisms could promote the replacement of donor parenchmal cells with recipient cells and contribute to vascuplopathy. This review discusses the interplay of platelets and the immune system in relation to transplantation.

Thrombin-dependent intravascular leukocyte trafficking regulated by fibrin and the platelet receptors GPIb and PAR4

“…Thus, through distinct molecular interactions, thrombin both promotes and retards leukocyte trafficking, suggesting that targeting thrombin's specific molecular interactions, rather than global anticoagulant treatment, could modulate thromboinflammation with reduced impact on haemostasis. Dysregulated blood coagulation, platelet activation and endothelial dysfunction are common features of a broad range of thromboinflammatory disorders, including ischaemiareperfusion injury 39 , venous thromboembolism 40 , thrombotic microangiopathies 41 and transplant rejection 42,43 . The experimental needle injury method used in this study has enabled detailed insight into the mechanisms by which dysregulated thrombin generation on the surface of procoagulant endothelial cells may influence intravascular leukocyte trafficking in vivo.…”

Platelets in Early Antibody-Mediated Rejection of Renal Transplants

“…The potential for platelets to participate in AMR has been recognized [18][19][20] but not tested in a relevant model of organ transplantation. Platelets are not easily observed with routine stains because of their small size and lack of nucleus.…”

Pathologic diagnosis of antibody-mediated rejection in endomyocardial biopsy after heart transplantation based on renewed International Society for Heart and Lung Transplantation criteria

“…Although, complement-activating alloantibodies have been connected with AMR, there are studies [8] that proved contribution of non-complement-activating alloantibody. In heart transplant recipients AMR is clinically associated with an increased expression of P-selectin and von Willebrand factor on the vascular endothelium [15], which lead to vascular inflammation and extensive aggregates of platelets that occlude the arteries, capillaries and veins [16,17]. This mechanism explains why AMR in heart EMB is usually referred to coronary allograft vasculopathy (CAV) and manifests as diffuse atherosclerosis with myointimal proliferation in the coronary arteries [9,11].…”