The Metalloprotease-Disintegrin ADAM8 Is Essential for the Development of Experimental Asthma

Silvia Nous, Marie-Renee Blanchet, Klaus Gossens, Colby Zaph, Joerg W. Bartsch, Kelly M. McNagny, Hermann J. Ziltener

Research output: Contribution to journalArticlepeer-review

55 Citations (Scopus)

Abstract

Rationale: Expression of the metalloprotease ADAM8 is increased in patients with asthma, but the functional significance of elevated ADAM8 expression in the context of asthma pathogenesis remains elusive. Objectives: To study development of asthma in ADAM8-deficient mice. Methods: Ovalbumin-induced asthma was studied in wild-type, ADAM8-deficient, and ADAM8-chimeric mice. Lung inflammation was assessed by histology, analysis of bronchoalveolar lavage, and airway hyperresponsiveness. Measurements and Main Results: ADAM8-deficient mice are highly resistant to the development of ovalbumin-induced airway inflammation and hyperresponsiveness. ADAM8 expression was induced in both hematopoietic cells and the nonhematopoietic microenvironment after induction of asthma, and ADAM8 expression in both cell populations was required for the full manifestation of asthma. Interestingly, loss of ADAM8 on T cells alone was sufficient to significantly decrease the asthma response. The attenuated response was not due to an intrinsic defect in antigen presentation or cytokine production but reflected an impaired migration of T cells, eosinophils, CD11b(+) CD11c(-), and CD11c(+) cells from blood vessels to the lung and alveolar space, suggesting a general hematopoietic cell deficiency in the absence of ADAM8. Conclusions: The results show that ADAM8 plays a proinflammatory role in airway inflammation. The milder disease outcome in the absence of ADAM8 suggests that this protein might be an interesting new target in treatment of this, and potentially other, inflammatory diseases in which recruitment of inflammatory cells is an essential part of pathogenesis.
Original languageEnglish
Pages (from-to)1318 - 1328
Number of pages11
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume181
Issue number12
DOIs
Publication statusPublished - 15 Jun 2010

Fingerprint

Dive into the research topics of 'The Metalloprotease-Disintegrin ADAM8 Is Essential for the Development of Experimental Asthma'. Together they form a unique fingerprint.

Cite this