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This work was supported by the Spanish Ministry of Health and ISCIII (co-financed by Fondos FEDER) (FIS-PI17-01819, FIS-PI20-01690, EuroNanoMed III AC17-0027, RD16/0012/0011); and by the project "Molecular stratification of patients with giant cell arthritis to tailor glucocorticoid and tocilizumab therapy (START Project)", funded by FOREUM, Foundation for Research in Rheumatology.

Analysis of institutional authors

Ramos-Manzano, AlejandraAuthorGarcia-Perez, JavierAuthorDe Vicuña, Rosario GarcíaAuthorVicente-Rabaneda, Esther FAuthorCastaneda, SantosCorresponding Author

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December 5, 2024
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Article

Low P-Selectin Glycoprotein Ligand-1 Expression in Neutrophils Associates with Disease Activity and Deregulated NET Formation in Systemic Lupus Erythematosus

Publicated to:INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. 24 (7): 6144- - 2023-04-01 24(7), DOI: 10.3390/ijms24076144

Authors: Munoz-Callejas, Antonio; Gonzalez-Sanchez, Elena; Silvan, Javier; Antonio, Esther San; Gonzalez-Tajuelo, Rafael; Ramos-Manzano, Alejandra; Sanchez-Abad, Ines; Gonzalez-Alvaro, Isidoro; Garcia-Perez, Javier; Tomero, Eva G; de Vicuna, Rosario Garcia; Vicente-Rabaneda, Esther F; Castaneda, Santos; Urzainqui, Ana

Affiliations

Hosp Princesa, Fdn Invest Biomed FIB, Immunol Dept, Inst Invest Sanitaria Princesa IIS Princesa, Madrid 28006, Spain - Author
Hosp Princesa, Fdn Invest Biomed FIB, Pulmonol Dept, Inst Invest Sanitaria Princesa IIS Princesa, Madrid 28006, Spain - Author
Hosp Princesa, Fdn Invest Biomed FIB, Rheumatol Dept, Inst Invest Sanitaria Princesa IIS Princesa, Madrid 28006, Spain - Author
Univ Autonoma Madrid, Dept Med, Catedra UAM Roche, EPID Future, Madrid 28049, Spain - Author

Abstract

Systemic Lupus Erythematosus (SLE) is an autoimmune disease characterized by the generation of anti-DNA autoantibodies due to exposure of immune cells to excessive amounts of extracellular DNA. Lack of P-selectin in mice induces the development of a lupus-like syndrome and patients with cutaneous lupus have reduced P-selectin expression in skin vessels. Using flow cytometry we analyzed in healthy donors and patients the expression of P-selectin Glycoprotein Ligand-1 (PSGL-1) in circulating neutrophils and the implication of PSGL-1/P-selectin interaction in neutrophil extracellular traps (NETs) generation. We found a statistical significance that neutrophils from active SLE patients have a reduced expression of PSGL-1 and low levels of PSGL-1 in neutrophils from SLE patients associated with the presence of anti-dsDNA antibodies, clinical lung involvement, Raynaud's phenomenon, and positive lupus anticoagulant. PSGL-1 is present along the DNA in the NET. In healthy donors, neutrophil interaction with immobilized P-selectin triggers Syk activation, increases the NETs percentage and reduces the amount of DNA extruded in the NETs. In active SLE patients, neutrophil interaction with P-selectin does not activate Syk or reduce the amount of DNA extruded in the NETs, that might contribute to increase the extracellular level of DNA and hence, to disease pathogenesis.

Keywords

netsp-selectinpsgl-1sle pathogenesisAdhesionAnimalsAutoimmune diseasesDnaExtracellular trap formationExtracellular trapsHumansIn-vitroInhibitorLupus erythematosus, systemicMiceNetNetsNeutrophilsP-selectinP-selectin ligand proteinPsgl-1QuantificationReceptorSle pathogenesisTargeTyrosine kinase syk

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2023, it was in position 66/313, thus managing to position itself as a Q1 (Primer Cuartil), in the category Biochemistry & Molecular Biology.

From a relative perspective, and based on the normalized impact indicator calculated from the Field Citation Ratio (FCR) of the Dimensions source, it yields a value of: 3.04, which indicates that, compared to works in the same discipline and in the same year of publication, it ranks as a work cited above average. (source consulted: Dimensions Jul 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-07-09, the following number of citations:

  • WoS: 5
  • Scopus: 8
  • Europe PMC: 2

Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-07-09:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 11.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 12 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 0.5.
  • The number of mentions on the social network X (formerly Twitter): 1 (Altmetric).

It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

  • The work has been submitted to a journal whose editorial policy allows open Open Access publication.

Leadership analysis of institutional authors

the author responsible for correspondence tasks has been CASTAÑEDA SANZ, SANTOS.