Autoren:	Gladigau, Gerd Haselmayer, Philipp Scharrer, Inge Munder, Markus Prinz, Nadine Lackner, Karl J. Schild, Hansjörg Stein, Pamela Radsak, Markus
Titel:	A role for Toll-like receptor mediated signals in neutrophils in the pathogenesis of the anti-phospholipid syndrome
Online-Publikationsdatum:	20-Okt-2022
Erscheinungsdatum:	2012
Sprache des Dokuments:	Englisch
Zusammenfassung/Abstract:	The anti-phospholipid syndrome (APS) is characterized by recurrent thrombosis and occurrence of anti-phospholipid antibodies (aPL). aPL are necessary, but not sufficient for the clinical manifestations of APS. Growing evidence suggests a role of innate immune cells, in particular polymorphonuclear neutrophils (PMN) and Toll-like receptors (TLR) to be additionally involved. aPL activate endothelial cells and monocytes through a TLR4-dependent signalling pathway. Whether this is also relevant for PMN in a similar way is currently not known. To address this issue, we used purified PMN from healthy donors and stimulated them in the presence or absence of human monoclonal aPL and the TLR4 agonist LPS monitoring neutrophil effector functions, namely the oxidative burst, phagocytosis, L-Selectin shedding and IL-8 production. aPL alone were only able to induce minor activation of PMN effector functions at high concentrations. However, in the additional presence of LPS the activation threshold was markedly lower indicating a synergistic activation pathway of aPL and TLR in PMN. In summary, our results indicate that PMN effector functions are directly activated by aPL and boosted by the additional presence of microbial products. This highlights a role for PMN as important innate immune effector cells that contribute to the pathophysiology of APS.
DDC-Sachgruppe:	610 Medizin 610 Medical sciences
Veröffentlichende Institution:	Johannes Gutenberg-Universität Mainz
Organisationseinheit:	FB 04 Medizin
Veröffentlichungsort:	Mainz
ROR:	https://ror.org/023b0x485
DOI:	http://doi.org/10.25358/openscience-8112
Version:	Published version
Publikationstyp:	Zeitschriftenaufsatz
Nutzungsrechte:	CC BY
Informationen zu den Nutzungsrechten:	https://creativecommons.org/licenses/by/3.0/
Zeitschrift:	PLoS one 7 7
Seitenzahl oder Artikelnummer:	1 9 e42176
Verlag:	PLoS
Verlagsort:	Lawrence, Kan.
Erscheinungsdatum:	2012
ISSN:	1932-6203
URL der Originalveröffentlichung:	http://dx.doi.org/10.1371/journal.pone.0042176
DOI der Originalveröffentlichung:	10.1371/journal.pone.0042176
Enthalten in den Sammlungen:	DFG-OA-Publizieren (2012 - 2017)