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Blood-Borne Microparticles Are an Inflammatory Stimulus in Type 2 Diabetes Mellitus.
Thom, Stephen R; Bhopale, Veena M; Arya, Awadhesh K; Ruhela, Deepa; Bhat, Abid R; Mitra, Nandita; Hoffstad, Ole; Malay, D Scot; Mirza, Ziad K; Lantis, John C; Lev-Tov, Hadar A; Kirsner, Robert S; Hsia, Ru-Ching; Levinson, Susan L; DiNubile, Mark J; Margolis, David J.
Afiliación
  • 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.
Immunohorizons ; 7(1): 71-80, 2023 01 01.
Article en En | MEDLINE | ID: mdl-36645851
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Diabetes Mellitus Tipo 2 Límite: Animals / Humans Idioma: En Revista: Immunohorizons Año: 2023 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Diabetes Mellitus Tipo 2 Límite: Animals / Humans Idioma: En Revista: Immunohorizons Año: 2023 Tipo del documento: Article Pais de publicación: Estados Unidos