concanavalin-a and Blood-Platelet-Disorders

The scavenger receptor CD36 recognizes a diverse set of ligands and has been implicated in a wide variety of normal and pathological processes, including lipid metabolism, angiogenesis, atherosclerosis, and phagocytosis. In particular, recent findings have demonstrated its crucial functions in sterile inflammation and tumor metastasis. However, the role of CD36 in immune-mediated hepatitis remains unclear. Concanavalin A (ConA)-induced liver injury is a well-established experimental T cell-mediated hepatitis. To understand the role of CD36 in hepatitis, we tested the susceptibility of CD36-deficient (CD36. Our findings suggest that CD36 plays an important proinflammatory role in ConA-induced liver injury by promoting hepatic inflammation and mediating the proapoptotic effect of chemokine CXCL10, and therefore, may be a potential therapeutic target for immune-mediated hepatitis. (Hepatology 2018;67:1943-1955).

Topics: Animals; Apoptosis; Blood Platelet Disorders; CD36 Antigens; Chemical and Drug Induced Liver Injury; Chemokine CXCL10; Concanavalin A; Cytokines; Disease Models, Animal; Flow Cytometry; Genetic Diseases, Inborn; Genistein; Hepatitis; Hepatocytes; Liver; Mice; Mice, Inbred C57BL; Signal Transduction

The composition of carbohydrates on the surface of platelets from a patient with Glanzmann's thrombasthenia and from seven normal donors were determined and compared. To this end, binding studies were performed using nine different purified 125I-labeled lectins; Concanavalin A, P-Phytohaemagglutinin, Wheat Germ Agglutinin, Dolichos biflorus, Pisum sativum, Ricinus communis II Agglutinin, Tetragonolobus purpureus, Lens culinaris and Soybean Agglutinin. These studies show that thrombasthenic platelets bear significantly decreased numbers of receptors for Concanavalin A and Lens culinaris, both with a specificity for D-mannose, and Ricinus communis II, with specificity for D-galactose. There were no detectable differences in the numbers of other lectin receptors. These results provide further evidence of molecular defects in thrombasthenic platelets. Moreover, the use of 125I-labeled lectins, as shown here, provides a fast and reliable technique for identifying abnormalities in the carbohydrate composition on the surface of platelets in various thrombopathies.

Topics: Blood Platelet Disorders; Blood Platelets; Carbohydrates; Concanavalin A; Galactose; Humans; Iodine Radioisotopes; Isotope Labeling; Kinetics; Lectins; Mannose; Phytohemagglutinins; Plant Lectins; Receptors, Mitogen; Soybean Proteins; Thrombasthenia; Wheat Germ Agglutinins

The authors report here the results of fracture-labeling of wheat germ agglutinin (WGA) and concanavalin A (Con A) receptors on the plasma membranes of normal, Bernard-Soulier, and thrombasthenic platelets. In all cases, virtually all of the label was confined to the exoplasmic half of the membrane. Despite the absence of GP Ib in Bernard-Soulier platelets and the absence or strong reduction of Gp IIb and GP IIIa in thrombasthenic platelets, their plasma membranes were strongly labeled by both Con A and WGA. These results are best accounted for by the presence of other glycoproteins and/or glycolipids at the platelet surface.

Topics: Adult; Bernard-Soulier Syndrome; Blood Platelet Disorders; Blood Platelets; Cell Membrane; Concanavalin A; Freeze Fracturing; Glycoproteins; Histocytochemistry; Humans; Lectins; Microscopy, Electron; Receptors, Concanavalin A; Receptors, Mitogen; Thrombasthenia; Wheat Germ Agglutinins

Concanavalin A was employed to study the role of platelet membrane glycoproteins in platelet-fibrin interactions during clot formation. A rheological technique was used to study the interactions, measuring the clot rigidity and platelet contractile force simultaneously during the formation of network structure. Concanavalin A lowered the clot rigidity and contractile force of a platelet-rich plasma clot by a small extent. Plasma glycoproteins probably compete with platelet membranes for concanavalin A binding in platelet-rich plasma. Both native concanavalin A (tetrameric) and succinyl concanavalin A (dimeric) lowered the clot rigidity and contractile force of a washed platelet-fibrin clot dramatically, almost down to those values found for fibrin clots. Inhibition studies with alpha-methyl-D-mannoside indicated that the concanavalin A effects were specific for the concanavalin A binding capacity to platelets. The effects of native concanavalin A on platelet-fibrin clots were only partially reversible, while the succinyl concanavalin A effects were completely reversible. The observed concanavalin A effects are probably mainly due to concanavalin A binding to platelet membrane glycoproteins. The concanavalin A binding site appears to play an important role in the fibrin binding to platelets.

Topics: Binding Sites; Blood Platelet Disorders; Blood Platelets; Cell Membrane; Concanavalin A; Fibrin; Fibrinogen; Humans; Kinetics; Macromolecular Substances; Receptors, Concanavalin A; Rheology

Topics: Blood Platelet Disorders; Blood Platelets; Concanavalin A; Humans; Lectins; Phytohemagglutinins; Protein Binding