Blood-Borne Microparticles Are an Inflammatory Stimulus in Type 2 Diabetes Mellitus.

Autor:	Thom SR; Department of Emergency Medicine, University of Maryland School of Medicine, Baltimore, MD., Bhopale VM; Department of Emergency Medicine, University of Maryland School of Medicine, Baltimore, MD., Arya AK; Department of Emergency Medicine, University of Maryland School of Medicine, Baltimore, MD., Ruhela D; Department of Emergency Medicine, University of Maryland School of Medicine, Baltimore, MD., Bhat AR; Department of Emergency Medicine, University of Maryland School of Medicine, Baltimore, MD., Mitra N; Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA., Hoffstad O; Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA., Malay DS; Department of Surgery, Penn Presbyterian Medical Center, Philadelphia, PA., Mirza ZK; MVS Wound Care and Hyperbarics, Towson, MD., Lantis JC; Department of Surgery, Icahn School of Medicine at Mount Sinai, New York City, NY., Lev-Tov HA; Dr. Phillip Frost Department of Dermatology and Cutaneous Surgery, University of Miami School of Medicine, Miami, FL., Kirsner RS; Dr. Phillip Frost Department of Dermatology and Cutaneous Surgery, University of Miami School of Medicine, Miami, FL., Hsia RC; Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD; and., Levinson SL; BioAegis Therapeutics, North Brunswick, NJ., DiNubile MJ; BioAegis Therapeutics, North Brunswick, NJ., Margolis DJ; Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
Jazyk:	angličtina
Zdroj:	ImmunoHorizons [Immunohorizons] 2023 Jan 01; Vol. 7 (1), pp. 71-80.
DOI:	10.4049/immunohorizons.2200099
Abstrakt:	The proinflammatory state associated with diabetes mellitus (DM) remains poorly understood. We found patients with DM have 3- to 14-fold elevations of blood-borne microparticles (MPs) that bind phalloidin (Ph; Ph positive [+] MPs), indicating the presence of F-actin on their surface. We hypothesized that F-actin-coated MPs were an unrecognized cause for DM-associated proinflammatory status. Ph+MPs, but not Ph-negative MPs, activate human and murine (Mus musculus) neutrophils through biophysical attributes of F-actin and membrane expression of phosphatidylserine (PS). Neutrophils respond to Ph+MPs via a linked membrane array, including the receptor for advanced glycation end products and CD36, PS-binding membrane receptors. These proteins in conjunction with TLR4 are coupled to NO synthase 1 adaptor protein (NOS1AP). Neutrophil activation occurs because of Ph+MPs causing elevations of NF-κB and Src kinase (SrcK) via a concurrent increased association of NO synthase 2 and SrcK with NOS1AP, resulting in SrcK S-nitrosylation. We conclude that NOS1AP links PS-binding receptors with intracellular regulatory proteins. Ph+MPs are alarmins present in normal human plasma and are increased in those with DM and especially those with DM and a lower-extremity ulcer. (Copyright © 2023 The Authors.)
Databáze:	MEDLINE
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