ArticleAmerican journal of respiratory cell and molecular biology2011
An obligate role for membrane-associated neutral sphingomyelinase activity in orienting chemotactic migration of human neutrophils.
Article in American journal of respiratory cell and molecular biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 28 citations in OpenAlex.
- Association of plasma ceramide with stroke-associated pneumonia in acute ischemic stroke.Frontiers in immunology · 2026Article
- Molecular mechanisms of KMT2C alterations in gastrointestinal cancers: enhancer network destabilization, lineage plasticity, and clinical translation.Frontiers in immunology · 2026Review
- Ceramide signaling in immunity: a molecular perspective.Lipids in health and disease · 2025Review
- Review
- Microbiota-induced active translocation of peptidoglycan across the intestinal barrier dictates its within-host dissemination.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- The Promotional Effect of GW4869 onPathogens (Basel, Switzerland) · 2022Article
- Sphingomyelin Depletion Inhibits CXCR4 Dynamics and CXCL12-Mediated Directed Cell Migration in Human T Cells.Frontiers in immunology · 2022Article
- Exosomes mediate LTB4 release during neutrophil chemotaxis.PLoS biology · 2021Article
- Differential Modulation of 25-hydroxycholecalciferol on Innate Immunity of Broiler Breeder Hens.Animals : an open access journal from MDPI · 2021Article
- β-Glucan-stimulated neutrophil secretion of IL-1α is independent of GSDMD and mediated through extracellular vesicles.Cell reports · 2021Article
- Sphingomyelin Breakdown in T Cells: Role of Membrane Compartmentalization in T Cell Signaling and Interference by a Pathogen.Frontiers in cell and developmental biology · 2019Review
- nSMase2 (Type 2-Neutral Sphingomyelinase) Deficiency or Inhibition by GW4869 Reduces Inflammation and Atherosclerosis in ApoeArteriosclerosis, thrombosis, and vascular biology · 2018Article
- The Many Facets of Sphingolipids in the Specific Phases of Acute Inflammatory Response.Mediators of inflammation · 2018Review
- Neutral sphingomyelinases control extracellular vesicles budding from the plasma membrane.Journal of extracellular vesicles · 2017Article
- The Activity of the Neutral Sphingomyelinase Is Important in T Cell Recruitment and Directional Migration.Frontiers in immunology · 2017Article
- Exosomes Mediate LTB4 Release during Neutrophil Chemotaxis.PLoS biology · 2016Article
- Roles and regulation of neutral sphingomyelinase-2 in cellular and pathological processes.Advances in biological regulation · 2015Review
- Regulation of mammalian physiology, development, and disease by the sphingosine 1-phosphate and lysophosphatidic acid receptors.Chemical reviews · 2011Review
- Drug targeting of sphingolipid metabolism: sphingomyelinases and ceramidases.British journal of pharmacology · 2011Review
- Improved detection of nicotinamide adenine dinucleotide phosphate oscillations within human neutrophils.Cytometry. Part A : the journal of the International Society for Analytical Cytology · 2010Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
For polymorphonuclear neutrophils (PMNs) to orient migration to chemotactic gradients, weak external asymmetries must be amplified into larger internal signaling gradients. Lipid mediators, associated with the plasma membrane and within the cell, participate in generating these gradients. This study examined the role in PMN chemotaxis of neutral sphingomyelinase (N-SMase), a plasma membrane-associated enzyme that converts sphingomyelin to ceramide. A noncompetitive N-SMase inhibitor, GW4869 (5 mM, 5 minutes), did not inhibit PMN motility (as percentage of motile cells, or mean cell velocity), but it abrogated any orientation of movement toward the source of the chemotaxin, formylmethionylleucylphenylanaline (FMLP) (net displacement along the gradient axis in micrometers, or as percentage of total migration distance). This defect could be completely reversed by treatment with lignoceric ceramide (5 μg/ml, 15 minutes). Immunolocalization studies demonstrated that N-SMase (1) distributes preferentially toward the leading edge of some elongated cells, (2) is associated with the plasma membrane, (3) is more than 99.5% localized to the cytofacial aspect of the plasma membrane, (4) is excluded from pseudopodial extensions, and (5) increases rapidly in response to FMLP. Morphologically, the inhibition of N-SMase limited cellular spreading and the extension of sheet-like pseudopods. Elongated PMNs demonstrated a polarized distribution of GTPases, with Rac 1/2 accumulated at, and RhoA excluded from, the front of the cell. This polarity was negated by N-SMase inhibition and restored by lignoceric ceramide. We conclude that N-SMase at the cytofacial plasma membrane is an essential element for the proper orientation of PMNs in FMLP gradients, at least in part by polarizing the distribution of Rac 1/2 and RhoA GTPases.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.