An HIV antibody (Ab) against platelet integrin GPIIIa49-66 induces complement-independent platelet particle formation by the elaboration of reactive oxygen species (ROS) downstream of the activation of the platelet NADPH oxidase by the 12-lipoxygenase (12-LO) product 12(S)-HETE. To determine whether other inducers of platelet particle formation also function via the induction of ROS, we examined the effects of the Ca(2+) ionophore A23187 and phorbol myristate acetate (PMA). Both agents induced oxidative platelet particle formation in an identical fashion as Ab, requiring Ca(2+) flux and 12(S)-HETE production as well as intact NADPH oxidase and 12-LO pathways. Since HIV-ITP patients with this Ab correct their platelet counts with dexamethasone (Dex), we examined the role of this steroid in this unique autoimmune disorder. Dex at therapeutic concentrations inhibited Ab-, A23187-, or PMA-induced platelet particle formation by inhibiting platelet PLA(2), 12-LO, and NADPH oxidase. The operational requirement of translocation of PLA(2), 12-LO, and NADPH oxidase components (p67 phox) from cytosol to membrane for induction of ROS was both inhibited and partially reversed by Dex in platelets. We conclude that (1) platelet particle formation can be induced by the generation of ROS; and (2) platelet PLA(2), 12-LO, NADPH oxidase, and cytosol membrane translocation, requirements for ROS production, are inhibited by Dex.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1976358 | PMC |
| http://dx.doi.org/10.1182/blood-2006-10-054064 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Pilot study characterizing a single pooled preparation of equine platelet lysate for nebulization in the horse.
Front Vet Sci
December 2024
Department of Clinical Sciences, College of Veterinary Medicine, Auburn University, Auburn, AL, United States.
Introduction: Platelet lysate (PL) demonstrates antimicrobial and anti-inflammatory properties offering potential for treatment of bacterial pneumonia in horses. It remains unknown whether nebulization is suitable for PL administration in horses. This pilot study characterized particle size and flow rate of pooled equine PL (single preparation) nebulized using an equine-specific nebulizer (Flexivent).
View Article and Find Full Text PDFBiomimetic Anisotropic-Functionalized Platelet-Membrane-Coated Polymeric Particles for Targeted Drug Delivery to Human Breast Cancer Cells.
ACS Appl Mater Interfaces
December 2024
Department of Biomedical Engineering, Translational Tissue Engineering Center, Johns Hopkins Translational ImmunoEngineering Center, and the Institute for Nanobiotechnology, Johns Hopkins School of Medicine, 400 N. Broadway, Smith Building 5017, Baltimore, Maryland 21231, United States.
Biomimetic particles that can replicate aspects of natural biological cell function are useful for advanced biological engineering applications. Engineering such particles requires mimicking the chemical complexity of the surface of biological cells, and this can be achieved by coating synthetic particles with naturally derived cell membranes. Past research has demonstrated the feasibility of utilizing cell membrane coatings from a variety of cell types to achieve extended blood circulation half-life.
View Article and Find Full Text PDFRecent developments in microfluidic passive separation to enable purification of platelets for transfusion.
Biomicrofluidics
December 2024
Department of Biomedical Engineering, University of Houston, Houston, Texas 77204, USA.
Platelet transfusion is a lifesaving therapy intended to prevent and treat bleeding. However, in addition to platelets, a typical unit also contains a large volume of supernatant that accumulates multiple pro-inflammatory contaminants, including residual leukocytes, microaggregates, microparticles, antibodies, and cytokines. Infusion of this supernatant is responsible for virtually all adverse reactions to platelet transfusions.
View Article and Find Full Text PDFRelevance of the Platelet-activating factor system in chemical warfare agents-induced effects.
Free Radic Biol Med
December 2024
Department of Pharmacology and Toxicology, Boonshoft School of Medicine Wright State University, Dayton, OH, 45435, USA. Electronic address:
The threats to chemical warfare-associated agents (CWA), including nitrogen mustard, are increasing, and no direct antidote is currently available to mitigate the deleterious cutaneous and systemic responses to prevent mortality. Though most of these agents act as alkylating agents, a significant knowledge gap exists in the molecular mechanisms of how these vesicants cause toxic effects. Studies, including ours, have shown that exposure to reactive oxygen species (ROS)-generating stimuli, including alkylating chemotherapeutic agents, and thermal burn injuries with ethanol produce the potent family of lipid mediators, Platelet-activating factor (PAF) agonists that induce local inflammation, and multi-system organ dysfunction (MOD).
View Article and Find Full Text PDFPlatelets as key cells in endometriosis patients: Insights from small extracellular vesicles in peritoneal fluid and endometriotic lesions analysis.
FASEB J
December 2024
Institute for Maternal and Child Health, IRCCS Burlo Garofolo, Trieste, Italy.
Endometriosis is a chronic inflammatory condition characterized by the presence of endometrium-like tissue outside the uterus, primarily affecting pelvic organs and tissues. In this study, we explored platelet activation in endometriosis. We utilized the STRING database to analyze the functional interactions among proteins previously identified in small extracellular vesicles (EVs) isolated from the peritoneal fluid of endometriosis patients and controls.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!