TY - JOUR A1 - Sehnert, Bettina A1 - Gierer, Philip A1 - Ibrahim, Saleh A1 - Kühl, Anja A1 - Voll, Reinhard A1 - Nandakumar, Kutty Selva A1 - Holmdahl, Rikard A1 - Hallmann, Rupert A1 - Vollmar, Brigitte A1 - Burkhardt, Harald T1 - Modulation of granulocyte-endothelium interactions by antileukoproteinase : inhibition of anti-type II collagen antibody-induced leukocyte attachment to the synovial endothelium T2 - Arthritis Research & Therapy N2 - Antileukoproteinase (ALP) is a physiological inhibitor of granulocytic serine proteases that has been shown to have anti-inflammatory properties in addition to its antiproteolytic activity. On the basis of its potential to block anti-collagen type II (CII) antibody-induced arthritis (CAIA) and to suppress the conformational activation of β2-integrins in leukocytes, the present study was undertaken to investigate its interference with leukocyte adherence to cytokine-activated endothelium. The potential of recombinant ALP to block the interactions of leukocytes with the endothelial lining was concomitantly investigated in vitro and in vivo. Thus, intravital fluorescence microscopic imaging of leukocyte rolling and firm adhesion to postcapillary venules were performed in the knee joints of DBA1/J mice after intravenous injection of anti-CII mAbs. An IL-1β-activated endothelial layer formed by a murine glomerular cell line (glEND.2) was used to assay the interaction with human leukocytes in vitro. Electromobility shift and luciferase reporter gene assays permitted the analysis of cytokine-induced activation of the NF-κB pathway. Fluorescence-activated cell sorting was applied to determine endothelial E-selectin expression. Leukocyte rolling and firm adhesion to the synovial endothelium in an early response to the anti-CII antibody transfer were significantly decreased in ALP-pretreated mice. Concomitantly, ALP suppressed the IL-1β-induced NF-κB activation and the upregulation of E-selectin expression in glEND.2 cells in vitro. These findings support the notion that the newly uncovered properties of ALP to interfere with cytokine signalling and upregulation of adhesion molecules in endothelial cells are likely to contribute to the therapeutic potential of ALP in immune-complex-induced tissue injury. Y1 - 2006 UR - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/2434 UR - https://nbn-resolving.org/urn:nbn:de:hebis:30-29701 N1 - © 2006 Sehnert et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. VL - 8 IS - R95 ER -