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Byline: Kin'ya Abe (1), Toru Arai (1), Masahide Mori (1), Hiroshi Kida (1), Sho Goya (1), Hiroto Matsuoka (1), Tadashi Osaki (1), Isao Tachibana (1), Seiji Hayashi (1) Abstract: The selectin family adhesion molecules exert a crucial role in accumulation of leukocytes at the site of inflammation. To test the biological effects of soluble selectin on lung inflammation, we introduced an expression plasmid vector of soluble selectin gene via HVJ-liposome into a murine model of LPS-induced lung injury. The myeloperoxidase activity in LPS-injected mice was suppressed by the in vivo injection of soluble P-selectin gene relative to control mice. On the contrary, soluble E- or L-selectin genes did not exert suppressive effects. Our observations suggest that P-selectin plays a crucial role in the initial steps of lung inflammation, and exogenous introduction of soluble P-selectin by in vivo gene transfer method may be a useful strategy for regulating inflammation of the lung. Author Affiliation: (1) Department of Molecular Medicine, Osaka University Medical School, 2-2 Yamada-oka, Suita-city, Osaka, 565--0871, Japan Article History: Registration Date: 30/09/2004

Byline: Michael S. Mulligan (1), Alex B. Lentsch (1), Thomas P. Shanley (1), Masayuki Miyasaka (2), Kent J. Johnson (1), Peter A. Ward (1) Abstract: Acute hemorrhagic lung injury occurs in humans with anti-GBM antibody (Goodpasture's syndrome), however, the mechanism of this injury is still largely unknown. To date, treatment has been confined to steroids and plasmaphoresis. Infusion of anti-GBM antibody into rats caused lung injury with intra-alveolar hemorrhage and intrapulmonary accumulation of neutrophils. Lung injury was dependent on the presence of neutrophils and complement and required both TNF[alpha] and IL-1. Experiments employing blocking antibodies to adhesion molecules demonstrated requirements for the [beta].sub.1 integrin VLA-4, [beta].sub.2 integrins LFA-1 and Mac-1, and L-selectin. The endothelial cell adhesion molecules, E-selectin and ICAM-1, were also required for the full development of lung injury. Inhibition of TNF[alpha] or IL-1 or adhesion molecules reduced both lung injury and tissue neutrophil accumulation. Thus, this study underscores cytokine and adhesion molecule requirements for neutrophil mediated injury in lung and kidney caused by anti-GBM, suggesting potential targets for the treatment of Goodpasture's syndrome in humans. Author Affiliation: (1) Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan, 48109 (2) Department of Bioregulation, Osaka University Medical School, Japan Article History: Registration Date: 03/10/2004

Byline: Steven H. Zuckerman (1), Jason Gustin (2), Glenn F. Evans (1) Abstract: Microglial cell activation plays a central role in acute and chronic inflammatory processes associated with neurodegeneration. As macrophage activation is generally associated with the up-regulation of specific surface antigens, the expression of CD54, and CD29 were evaluated on CD11b positive neonatal rat microglial cell cultures by flow cytometry. These cells when exposed to lipopolysaccharide, LPS, and gamma interferon, IFNI3, exhibited a 2--3 fold increase in CD54 expression, an increase in CD29 and no change in CD11b. Maximal increases in CD54 and CD29 staining on CD11b positive microglial cells were apparent 20--24 h after LPS and IFNI3 while nitrite production reflecting inducible nitric oxide synthase activity, continued to increase. The increases in CD29 and CD54 staining were inhibited in a dose dependent manner by agents which increased intracellular cAMP levels including 100 uM 8-bromoadenosine 3 :5 -cyclic monophosphate but not 8-bromoadenosine monophosphate, the phosphodiesterase inhibitor isobutyl methylxanthine and by direct activation of adenylate cyclase with forskolin. Concomitant with the dose dependent decreases in CD29 and CD54 staining were increases in intracellular cAMP and reduced TNF secretion. These results suggest that regulation of CD29 and CD54 expression on activated microglial cells involves a cAMP dependent pathway. Author Affiliation: (1) Division of Cardiovascular Research, Lilly Research Labs, Indianapolis, Indiana, 46285 (2) Department of Biology, DePauw University, Greencastle, Indiana Article History: Registration Date: 03/10/2004

The effect of receptor clustering on vesicle-vesicle adhesion was studied by creating rafts of synthetic cell adhesion molecules (CAMs) in the membrane of vesicles. These simple mimics of cells would be crosslinked through relatively weak Cu(iminodiacetate)-histidine bonds and these receptor clustering will enhance these individually weak links.

VLO5, EO5, and EC3 are the non-RGD-containing disintegrins that belong to the hetrodimeric family of snake venom-derived proteins. They are potent inhibitors of certain leukocyte integrins such as alpha4beta1, alpha4beta7 and alpha9beta1, and act through the MLD motif present in one of their subunits.

Previous research as shown that the extracellular matrix protein mindin contributes to allergic airways disease, but the role of mindin in non-allergic airways disease has not been explored. To test [...]

Inflammatory bowel diseases (IBDs) are chronic, remitting inflammatory conditions whose overall etiology is poorly understood and multifactorial. Recent studies have indicated that cadherin adhesion molecules have a role in IBDs. [...]