Mast cell extracellular trap formation underlies vascular and neural injury and hyperalgesia in sickle cell disease.

Autor:	Argueta DA; https://ror.org/04gyf1771 Division of Hematology/Oncology, Department of Medicine, University of California, Irvine, Irvine, CA, USA., Tran H; Division of Hematology, Oncology, and Transplantation, School of Medicine, University of Minnesota, Twin Cities, Minneapolis, MN, USA., Goel Y; https://ror.org/04gyf1771 Division of Hematology/Oncology, Department of Medicine, University of California, Irvine, Irvine, CA, USA., Nguyen A; Division of Hematology, Oncology, and Transplantation, School of Medicine, University of Minnesota, Twin Cities, Minneapolis, MN, USA., Nguyen J; Division of Hematology, Oncology, and Transplantation, School of Medicine, University of Minnesota, Twin Cities, Minneapolis, MN, USA., Kiven SB; https://ror.org/04gyf1771 Division of Hematology/Oncology, Department of Medicine, University of California, Irvine, Irvine, CA, USA., Chen C; Division of Hematology, Oncology, and Transplantation, School of Medicine, University of Minnesota, Twin Cities, Minneapolis, MN, USA., Abdulla F; Division of Hematology, Oncology, and Transplantation, School of Medicine, University of Minnesota, Twin Cities, Minneapolis, MN, USA., Vercellotti GM; Division of Hematology, Oncology, and Transplantation, School of Medicine, University of Minnesota, Twin Cities, Minneapolis, MN, USA., Belcher JD; Division of Hematology, Oncology, and Transplantation, School of Medicine, University of Minnesota, Twin Cities, Minneapolis, MN, USA., Gupta K; https://ror.org/04gyf1771 Division of Hematology/Oncology, Department of Medicine, University of California, Irvine, Irvine, CA, USA kalpnag@hs.uci.edu.; Division of Hematology, Oncology, and Transplantation, School of Medicine, University of Minnesota, Twin Cities, Minneapolis, MN, USA.
Jazyk:	angličtina
Zdroj:	Life science alliance [Life Sci Alliance] 2024 Sep 06; Vol. 7 (11). Date of Electronic Publication: 2024 Sep 06 (Print Publication: 2024).
DOI:	10.26508/lsa.202402788
Abstrakt:	Sickle cell disease (SCD) is the most common inherited monogenetic disorder. Chronic and acute pain are hallmark features of SCD involving neural and vascular injury and inflammation. Mast cells reside in the vicinity of nerve fibers and vasculature, but how they influence these structures remains unknown. We therefore examined the mechanism of mast cell activation in a sickle microenvironment replete with cell-free heme and inflammation. Mast cells exposed to this environment showed an explosion of nuclear contents with the release of citrullinated histones, suggestive of mast cell extracellular trap (MCET) release. MCETs interacted directly with the vasculature and nerve fibers, a cause of vascular and neural injury in sickle cell mice. MCET formation was dependent upon peptidylarginine deiminase 4 (PAD4). Inhibition of PAD4 ameliorated vasoocclusion, chronic and acute hyperalgesia, and inflammation in sickle mice. PAD4 activation may also underlie neutrophil trap formation in SCD, thus providing a novel target to treat the sequelae of vascular and neural injury in SCD. (© 2024 Argueta et al.)
Databáze:	MEDLINE
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