In the pulmonary circulation, endotoxemia induces leukocyte/endothelium interaction in pulmonary arterioles and venules. Thus, leukocytes may contribute to the pathogenesis of acute lung injury. In order to investigate, whether this interaction can be inhibited by early blockade of the adhesion cascade, we studied the effect of the humanized anti-L-selectin antibody HuDreg 200 on leukocyte kinetics in pulmonary arterioles and venules following i.v.-infusion of endotoxin. In endotoxemia HuDreg 200 reduces sticking of leukocytes in both pulmonary arterioles and venules. Thus, we were able to demonstrate that early blockade of the adhesion cascade effectively prevents leukocyte accumulation in pulmonary microvessels in endotoxemia. Therefore, HuDreg 200 may exhibit protective effects on the manifestation of leukocyte-mediated acute lung injury.
Download full-text PDF |
Source |
|---|
Publication Analysis
Top Keywords
Similar Publications
[Effect of humanised anti-L- selectin antibody HuDreg 200 on leukocyte kinetics in pulmonary microcirculation in endotoxinemia].
Langenbecks Arch Chir Suppl Kongressbd
November 2003
Institut für Chirurgische Forschung, Klinikum Grosshadern, Ludwig-Maximilians-Universität München.
In the pulmonary circulation, endotoxemia induces leukocyte/endothelium interaction in pulmonary arterioles and venules. Thus, leukocytes may contribute to the pathogenesis of acute lung injury. In order to investigate, whether this interaction can be inhibited by early blockade of the adhesion cascade, we studied the effect of the humanized anti-L-selectin antibody HuDreg 200 on leukocyte kinetics in pulmonary arterioles and venules following i.
View Article and Find Full Text PDFThe effect of trauma on neutrophil L-selectin expression and sL-selectin serum levels.
Shock
April 2001
Unfallchirurgische Klinik, Medizinische Hochschule Hannover, FRG.
Among identified adhesion molecules, the L-selectin on neutrophils enables the first step of leukocyte adherence to activated endothelial cells. To allow firm adhesion of neutrophils, L-selectin is then split off the cell membrane. It was hypothetized that an increase of the constitutively high serum level of soluble L-selectin may indicate an ongoing pathological neutrophil sequestration to the endothelial cells associated with activation and injury of the cells.
View Article and Find Full Text PDFRole of L-selectin in leukocyte sequestration in lung capillaries in a rabbit model of endotoxemia.
Am J Respir Crit Care Med
January 2000
Institute for Surgical Research and Department of Anesthesiology, University of Munich, Germany.
After a variety of pathophysiologic stimuli, neutrophils accumulate in lung capillaries and contribute to the pathogenesis of acute lung injury. Lung neutrophil sequestration has previously been attributed to mechanical retention of stiffened neutrophils, but L-selectin-mediated leukocyte/endothelial interaction may be an essential step. We investigated the effect of the anti-L-selectin antibody HuDreg 200 on leukocyte sequestration and microhemodynamics in alveolar capillaries in a model of acute endotoxemia.
View Article and Find Full Text PDFProperties and pharmacokinetics of two humanized antibodies specific for L-selectin.
Immunotechnology
March 1999
Protein Design Labs, Inc., Fremont, CA 94555, USA.
Background: The participation of L-selectin in leukocyte recruitment during inflammation has suggested the use of L-selectin inhibitors as potential anti-inflammatory therapeutics. Blocking monoclonal antibodies could serve as such therapeutic agents, particularly if humanized to reduce their immunogenicity and improve their serum half-life.
Objectives: For this purpose, two mouse monoclonal antibodies, DREG-55 and DREG-200, that block human L-selectin were humanized and characterized.
Fine mapping of the epitopes of humanized anti-L-selectin monoclonal antibodies HuDREG-55 and HuDREG-200.
Immunol Lett
November 1997
Protein Design Labs Incorporated, Mountain View, CA 94043, USA.
Blocking the function of L-selectin with a monoclonal antibody (mAb) is a promising way to prevent neutrophils from causing tissue damage during inflammation. HuDREG-55 and HuDREG-200 are humanized mAb which bind to human L-selectin and block its function as an adhesion molecule. To understand the mechanism of the action of HuDREG-55 and HuDREG-200, we determined their epitopes on L-selectin at the amino acid level.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!