X-ray irradiation effectively inactivated lymphocytes in transfusion in vivo monitored by the bioluminescence transfusion-associated graft-versus-host disease model.

BACKGROUND AND OBJECTIVES: Transfusion of cold-stored whole blood is the preferred resuscitation method for trauma patients but may cause transfusion-associated graft-versus-host disease (TA-GVHD). Standard clinical practice to prevent this is to irradiate blood components with gamma-rays. X-ray irradiations are also a safe and effective alternative to gamma-ray irradiation. We established a visual mouse model of TA-GVHD to compare the viability and function of lymphocytes exposed to gamma- and x-ray irradiation. MATERIALS AND METHODS: A haploidentical transplantation mouse model was established to simulate TA-GVHD with Balb/c mice as donors and hybrid F1 CB6 mice (Balb/c × C57) as recipients. Spleen cells from Tg-Fluc+ Balb/c mice were isolated and irradiated with gamma-rays and x-rays. Lymphocyte activation, apoptosis and proliferation post phorbol 1 2-myristate 1 3-acetate (PMA) stimulation were evaluated. After transfusion, we monitored Fluc+ lymphocytes daily by bioluminescence imaging. Recipients were euthanized on day 21, and tissues were examined pathologically and for inflammatory cytokines. RESULTS: The viability of gamma- or x-ray irradiated lymphocytes decreased significantly with slight changes in proliferation in vivo after transfusion. Compared with the non-irradiated group, both the gamma- and x-ray irradiated groups showed significantly decreased clinical scoring and inflammatory cytokine levels. The fluorescence intensity of the body and target organs was reduced after irradiation. CONCLUSION: No recipients acquired TA-GVHD after lymphocyte transfusion subjected to gamma- or x-rays, showing that x-rays inactivate as well as gamma rays and are suitable for irradiating whole blood.

Hemin regulates platelet clearance in hemolytic disease by binding to GPIbα.

Hemolysis is associated with thrombosis and vascular dysfunction, which are the pathological components of many diseases. Hemolytic products, including hemoglobin and hemin, activate platelets (PLT). Despite its activation, the effect of hemolysis on platelet clearance remains unclear, It is critical to maintain a normal platelet count and ensure that circulating platelets are functionally viable. In this study, we used hemin, a degradation product of hemoglobin, as a potent agonist to treat platelets and simulate changes in vivo in mice. Hemin treatment induced activation and morphological changes in platelets, including an increase in intracellular Ca2+ levels, phosphatidylserine (PS) exposure, and cytoskeletal rearrangement. Fewer hemin-treated platelets were cleared by macrophages in the liver after transfusion than untreated platelets. Hemin bound to glycoprotein Ibα (GPIbα), the surface receptor in hemin-induced platelet activation and aggregation. Furthermore, hemin decreased GPIbα desialylation, as evidenced by reduced Ricinus communis agglutinin I (RCA- I) binding, which likely extended the lifetime of such platelets in vivo. These data provided new insight into the mechanisms of GPIbα-mediated platelet activation and clearance in hemolytic disease.

What is the context? Hemolysis is a primary hematological disease. Hemolysis is a pathological complication of several diseases.Hemin, a degradation product of cell-free hemoglobin, has been proven to be a more potent agonist than hemoglobin for directly activating platelets.Platelet membrane glycoproteins (GP), including GPIb-IX and GPIIb/IIIa complexes, play crucial roles in platelet hemostasis.Desialylation (loss of sialic acid residues) of GPIbα, is believed to regulate physiological platelet clearance through liver macrophages and hepatocytes.What is new? In this study, we evaluated the effects of hemolysis on platelet clearance. We first analyzed the influence of hemin at 0-50 µM on platelets in vitro before exploring the mechanism underlying hemin-induced platelet activation and its role in platelet clearance in vitro and in vivo.Our analyses suggest that: Hemin bound to GPIbα on the platelet surface with high affinity.Platelet clearance occurred slowly in the liver and spleen after hemin treatment.Platelets exhibited significant significantly reduced GPIbα surface expression and desialylation after hemin treatment.Platelets exhibited significant significantly reduced GPIbα surface expression and desialylation after hemin treatment.What is the impact? This study provides new insights into the role of hemin in the mechanisms of GPIbα-mediated platelets activation and clearance in diseases associated with hemolysis.

Current Advances in Nanomaterials Affecting Functions and Morphology of Platelets.

Nanomaterials have been extensively used in the biomedical field due to their unique physical and chemical properties. They promise wide applications in the diagnosis, prevention, and treatment of diseases. Nanodrugs are generally transported to target tissues or organs by coupling targeting molecules or enhanced permeability and retention effect (EPR) passively. As intravenous injection is the most common means of administration of nanomedicine, the transport process inevitably involves the interactions between nanoparticles (NPs) and blood cells. Platelets are known to not only play a critical role in normal coagulation by performing adhesion, aggregation, release, and contraction functions, but also be associated with pathological thrombosis, tumor metastasis, inflammation, and immune reactions, making it necessary to investigate the effects of NPs on platelet function during transport, particularly the way in which their physical and chemical properties determine their interaction with platelets and the underlying mechanisms by which they activate and induce platelet aggregation. However, such data are lacking. This review is intended to summarize the effects of NPs on platelet activation, aggregation, release, and apoptosis, as well as their effects on membrane proteins and morphology in order to shed light on such key issues as how to reduce their adverse reactions in the blood system, which should be taken into consideration in NP engineering.