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PAR1 biased signaling is required for activated protein C in vivo benefits in sepsis and stroke
Activated protein C (APC) cleaves protease-activated receptor 1 (PAR1) in vitro at R46 to initiate beneficial cell signaling; however, thrombin and APC can cleave at R41. To elucidate PAR1-dependent aspects of the pharmacologic in vivo mechanisms of APC, we generated C57BL/6 mouse strains carrying QQ41 or QQ46 point mutations in PAR1 (F2r gene). Using these strains, we determined whether or not recombinant murine signaling-selective APC mutants would reduce septic death or provide neuroprotection against ischemic stroke when mice carried PAR1-homozygous mutations that prevent cleavage at either R41 or R46. Intercrossing PA...
Source: Blood - March 15, 2018 Category: Hematology Authors: Sinha, R. K., Wang, Y., Zhao, Z., Xu, X., Burnier, L., Gupta, N., Fernandez, J. A., Martin, G., Kupriyanov, S., Mosnier, L. O., Zlokovic, B. V., Griffin, J. H. Tags: Plenary Papers, Thrombosis and Hemostasis, Vascular Biology Source Type: research

A Polymorphism in Toll-like Receptor 2 Gene Is Associated with Occurrence of Bacterial Infections in Sickle Cell Disease Patients
Discussion: In SCD pts, TLR-2 rs4696480 TA genotype might be protective against bacterial infections, whereas TT genotype might increase risk of such infections. Previous reports demonstrated higher secretion of inflammatory factors in cells from AA individuals, lower occurrence and severity of immune diseases in T carriers. TA genotype might stand between deleterious effects of over inflammatory response (AA genotype) and under response (TT genotype) to infectious agents.DisclosuresNo relevant conflicts of interest to declare.
Source: Blood - November 21, 2018 Category: Hematology Authors: Tozatto-Maio, K., Girot, R., Ly, I. D., Rocha, V., Pinto, A. C. S., Diagne, I., Benzerara, Y., Dinardo, C. L., Kashima, S., Araujo, I. L., Kenzey, C., Fonseca, G. H. H., Rodrigues, E., Volt, F., Jarduli, L. R., Ruggeri, A., Mariaselvam, C. M., Gualandro, Tags: 113. Hemoglobinopathies, Excluding Thalassemia-Basic and Translational Science: Poster III Source Type: research