Dipeptidyl peptidase I-dependent neutrophil recruitment modulates the inflammatory response to Sendai virus infection. J Immunol 2008 Mar 01;180(5):3535-42
Date
02/23/2008Pubmed ID
18292580Pubmed Central ID
PMC2597084DOI
10.4049/jimmunol.180.5.3535Scopus ID
2-s2.0-49149112182 (requires institutional sign-in at Scopus site) 43 CitationsAbstract
The role of innate immunity in the pathogenesis of asthma is unclear. Although increased presence of neutrophils is associated with persistent asthma and asthma exacerbations, how neutrophils participate in the pathogenesis of asthma remains controversial. In this study, we show that the absence of dipeptidyl peptidase I (DPPI), a lysosomal cysteine protease found in neutrophils, dampens the acute inflammatory response and the subsequent mucous cell metaplasia that accompanies the asthma phenotype induced by Sendai virus infection. This attenuated phenotype is accompanied by a significant decrease in the accumulation of neutrophils and the local production of CXCL2, TNF, IL-1beta, and IL-6 in the lung of infected DPPI-/- mice. Adoptive transfer of DPPI-sufficient neutrophils into DPPI-/- mice restored the levels of CXCL2 and enhanced cytokine production on day 4 postinfection and subsequent mucous cell metaplasia on day 21 postinfection. These results indicate that DPPI and neutrophils play a critical role in Sendai virus-induced asthma phenotype as a result of a DPPI-dependent neutrophil recruitment and cytokine response.
Author List
Akk AM, Simmons PM, Chan HW, Agapov E, Holtzman MJ, Grayson MH, Pham CTMESH terms used to index this publication - Major topics in bold
AnimalsAsthma
Cathepsin C
Inflammation
Male
Metaplasia
Mice
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Neutrophil Infiltration
Neutrophils
Respiratory Mucosa
Respirovirus Infections
Sendai virus
T-Lymphocytes, Cytotoxic
