a role for toll-like receptor mediated signals in neutrophils in the pathogenesis of the anti-phospholipid syndrometoll样受体的作用在中性粒细胞介导信号anti-phospholipid综合症的发病机制.pdfVIP

A Role for Toll-Like Receptor Mediated Signals in Neutrophils in the Pathogenesis of the Anti- Phospholipid Syndrome 1 1¤ 2 2 3 3 Gerd Gladigau , Philipp Haselmayer , Inge Scharrer , Markus Munder , Nadine Prinz , Karl Lackner , ¨ 1 1 1,2 Hansjorg Schild , Pamela Stein *, Markus P. Radsak * 1 Institute of Immunology, Johannes Gutenberg-University Medical Center, Mainz, Germany, 2 Third Department of Medicine, Johannes Gutenberg-University Medical Center, Mainz, Germany, 3 Institute of Clinical Chemistry and Laboratory Medicine, Johannes Gutenberg-University Medical Center, Mainz, Germany 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 eff