Caspase-1-Deficient Mice Have Delayed Neutrophil Apoptosis and a Prolonged Inflammatory Response to Lipopolysaccharide-Induced Acute Lung Injury

• DOI: 10.4049/jimmunol.169.11.6401
• Publication Date: 2014-04-20T23:41:24Z
• Authors: Sarah J. Rowe; Lucy Allen; Victoria C. Ridger; Paul G. Hellewell; Moira K. B. Whyte
• Keywords: Proinflammatory cytokine

Abstract Caspase-1, the prototypic caspase, is known to process cytokines IL-1β and IL-18 mature forms but it unclear whether, like other caspases, can induce apoptosis by activation of downstream protease cascades. Neutrophils are express caspase-1, release undergo rapid, caspase-dependent apoptosis. We examined production in peripheral blood neutrophils caspase-1-deficient wild-type mice. Constitutive was delayed compared with LPS-mediated inhibition absent, were susceptible Fas-mediated LPS-stimulated absent from neutrophils. To ascertain whether these differences would alter response acute lung injury, we studied pulmonary neutrophil accumulation following intratracheal administration LPS. Caspase-1-deficient mice showed increased, predominantly neutrophilic inflammation, inflammation had resolved both deficient animals 72 h after LPS instillation. increased lungs also detected conclude that caspase-1 modulates inflammatory neutrophils, not essential for lung.