Platelet-activating factor and Escherichia coliO157:H7 infections.

The role of platelet-activating factor (PAF), a phospholipid inflammatory mediator, in Escherichia coli O157:H7-associated hemolytic uremic syndrome (HUS) is unknown. PAF is synthesized by diverse cells and is degraded by PAF-acetylhydrolase (PAF-AH). Deficient PAF-AH activity results from a G-->T transversion at position 994 of exon 9.

Tryptase inhibition blocks airway inflammation in a mouse asthma model.

Release of human lung mast cell tryptase may be important in the pathophysiology of asthma. We examined the effect of the reversible, nonelectrophilic tryptase inhibitor MOL 6131 on airway inflammation and hyper-reactivity in a murine model of asthma. MOL 6131 is a potent selective nonpeptide inhibitor of human lung mast cell tryptase based upon a beta-strand template (K(i) = 45 nM) that does not inhibit trypsin (K(i) = 1,061 nM), thrombin (K(i) = 23, 640 nM), or other serine proteases.

A role for cysteinyl leukotrienes in airway remodeling in a mouse asthma model.

Airway inflammation and remodeling in chronic asthma are characterized by airway eosinophilia, hyperplasia of goblet cells and smooth muscle, and subepithelial fibrosis. We examined the role of leukotrienes in a mouse model of allergen-induced chronic lung inflammation and fibrosis. BALB/c mice, after intraperitoneal ovalbumin (OVA) sensitization on Days 0 and 14, received intranasal OVA periodically Days 14-75.