Toll-like receptor expression and functional behavior in platelets from Systemic Lupus Erythematosus patients

Registro completo

Título

Toll-like receptor expression and functional behavior in platelets from Systemic Lupus Erythematosus patients

Autor(es)

Baroni Pietto, Maria Constanza; Glembotsky, Ana Claudia; Lev, Paola Roxana; Marin Oyarzún, Cecilia Paola; de Luca, Geraldine; Charó, Nancy Lorena; Cellucci, Adela Soledad; Heller, Paula Graciela; Goette, Nora Paula; Gomez, Graciela Noemi; Marta, Rosana Fernanda

Afiliación(es) del/de los autor(es)

Baroni Pietto, Maria Constanza. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina
Glembotsky, Ana Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina
Lev, Paola Roxana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina
Marin Oyarzún, Cecilia Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina
de Luca, Geraldine. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina
Charó, Nancy Lorena. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Cellucci, Adela Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina
Heller, Paula Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina
Goette, Nora Paula. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina
Gomez, Graciela Noemi. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina
Marta, Rosana Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina

Resumen

Abstract Background: Multiple blood cell abnormalities participate in the development of inflammation in systemic lupus erythematosus (SLE). Although platelets were pointed as one of these contributors through the release of their content during activation, there is scarce specific data about their role as immune players in SLE. Materials and Methods: Thirteen SLE patients were included. Toll-like receptor (TLR) 2, 4 and 9 were evaluated in resting platelets, while platelet-activation markers (PAC-1 binding, P-selectin, CD63 and CD40 ligand -L) and platelet-leukocyte aggregates were measured before and after specific TLR stimulation, by flow cytometry. Soluble CD40L and von Willebrand factor (vWf) release from stimulated platelets was measured by ELISA. Results: In resting conditions, TLR levels were normally expressed in SLE platelets. Platelet surface activation markers, soluble CD40L and vWf release were normal at baseline and after TLR stimulation. In contrast to normal samples behavior, platelet-monocyte aggregates in SLE were elevated in resting conditions and barely increased after TLR stimulation, while basal and stimulated platelet-neutrophil and platelet-lymphocyte aggregates in SLE samples were normal. C-reactive protein levels positively correlated with platelet-monocyte aggregates, at baseline and after stimulation with the TLR-2 agonist PAM3CSK4, suggesting these complexes could reflect the inflammatory activity in SLE. In this cohort 12 from 13 patients were under hydroxychloroquine (HCQ) treatment, a known inhibitor of endosomal activity and a potential inhibitor of platelet activation. The fact that SLE platelets responded normally to TLR agonists suggest that, in spite of this treatment, they are able to respond to increased damage-associated molecular patters (DAMPs) present in circulation from SLE patients. Interestingly, increased plasmatic levels of High Mobility Group Box 1 (HMGB1), a known DAMP, correlated with vWf release from TLR-stimulated platelets, suggesting HMGB1 could be also released by platelets, generating a positive platelet activation feedback loop that contribute to inflammation. Conclusion: This study shows normal platelet TLR expression and function, increased circulating platelet-monocyte aggregates and a direct correlation between plasmatic HMGB1 levels and platelet vWf release after TLR2 stimulation. This platelet behavior in a group of patients who are under HCQ, suggests platelets participate in the inflammatory state of SLE.

Año de publicación

2023

Idioma

español

Formato (Tipo MIME)

application/vnd.openxmlformats-officedocument.spreadsheetml.sheet

Clasificación temática de acuerdo a la FORD

Medicina básica

Condiciones de uso

Disponible en acceso abierto bajo licencia Creative Commons https://creativecommons.org/licenses/by-nc-nd/2.5/ar/

Repositorio digital

CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas

Identificador de proyecto

Ministerio de Ciencia. Tecnología e Innovación Productiva. Agencia Nacional de Promoción Científica y Tecnológica/PICT2017 Nº1288