The elevation of intracellular cyclic AMP by phosphodiesterase (PDE)4 inhibitors in eosinophils is associated with inhibition of the activation and recruitment of these cells. We have previously shown that systemic treatment with the PDE4 inhibitor rolipram effectively inhibit eosinophil migration in guinea pig skin. In the present study we compare the oral potency and efficacy of the PDE4 inhi...

Secretoneurin (SN), a 33-amino acid neuropeptide, is derived from secretogranin II that is released from sensory afferent C-fibers by capsaicin. Described functions of secretoneurin include chemotaxis of monocytes and endothelial cells, and inhibition of endothelial cell proliferation. Inhibition of monocyte chemotaxis by staurosporine indicated involvement of specific signaling pathways. We ha...

FIGURE 2 Dose-dependent effect of lipopolysaccharide (LPS) on neutrophil-induced trans-basement membrane migration of eosinophils in healthy volunteers. Neutrophils (2×10 cells) were stimulated with various concentrations of LPS (0.01–100 μg·mL) and then placed into the lower compartment. Eosinophils (1×10 cells) were added to the upper compartment of a chamber with a Matrigel-coated Transwell ...

Background: Clearance of tissue granulocytes is central to the resolution of airway inflammation. To date the focus has been on apoptotic mechanisms of cell removal and little attention has been given to alternative processes. The present study explores transepithelial migration as a mechanism of cell clearance. Method: Guinea pig tracheobronchial airways where eosinophils are constitutively pr...

PURPOSE Glucocorticoids can either suppress gene transcription (transrepression) or activate it (transactivation). This latter process may contribute to certain side effects caused by these agents. Mapracorat (also known as BOL-303242-X or ZK 245186) is a novel selective glucocorticoid receptor agonist that maintains a beneficial anti-inflammatory activity but seems to be less effective in tran...

UNLABELLED During lymphocyte migration, engagement of VCAM-1 stimulates the generation of endothelial cell-derived reactive oxygen species (ROS) and activation of matrix metalloproteinases, facilitating endothelial retraction. Because bilirubin is a potent antioxidant, we examined the hypothesis that this bile pigment inhibits VCAM-1-dependent cellular events. The migration of isolated murine s...

BACKGROUND Clearance of tissue granulocytes is central to the resolution of airway inflammation. To date the focus has been on apoptotic mechanisms of cell removal and little attention has been given to alternative processes. The present study explores transepithelial migration as a mechanism of cell clearance. METHOD Guinea pig tracheobronchial airways where eosinophils are constitutively pr...

Directional migration of leukocytes is an essential step in leukocyte trafficking during inflammatory responses. However, the molecular mechanisms governing directional chemotaxis of leukocytes remain poorly understood. The Slit family of guidance cues has been implicated for inhibition of leuocyte migration. We report that Clara cells in the bronchial epithelium secreted Slit2, whereas eosinop...