Epilysin (MMP-28) restrains early macrophage recruitment in Pseudomonas aeruginosa pneumonia

Anne M Manicone, Timothy P Birkland, Michelle Lin, Tomoko Betsuyaku, Nico van Rooijen, Jouko Lohi, Jorma Keski-Oja, Ying Wang, Shawn J Skerrett, William C Parks

    Research output: Contribution to journalArticleScientificpeer-review

    Abstract

    Several members of the matrix metalloproteinase (MMP) family function in various processes of innate immunity, particularly in controlling leukocyte influx. Epilysin (MMP-28) is expressed in numerous tissues and, in adult mice, it has the highest expression in lung, where it is detected in bronchial epithelial cells (Clara cells). Epilysin is also expressed by bone marrow-derived macrophages, but not by alveolar macrophages, suggesting that its expression by macrophages is dependent on localization and differentiation. To assess the role of this MMP, we generated epilysin-null (Mmp28(-/-)) mice. Although epilysin is constitutively expressed in normal tissues, Mmp28(-/-) mice have no overt phenotype. However, using a murine model of Pseudomonas aeruginosa pneumonia, we found that Minp28(-/-) mice had an early increase in macrophage recruitment into the lungs, as well as enhanced bacterial clearance and reduced pulmonary neutrophilia, which we predicted were due to accelerated macrophage influx. Macrophage depletion in WT and Mmp28(-/-) mice confirmed a role for macrophages in clearing P. aeruginosa and regulating neutrophil recruitment. Furthermore, we observed that macrophages derived from Minp28(-/-) mice migrated faster than did wildtype cells to bronchoalveolar lavage fluid from P. aeruginosa-treated mice of either genotype. These observations indicate that epilysin functions as an intrinsic negative regulator of macrophage recruitment by retarding the chemotaxis of these cells. The Journal of Immunology, 2009, 182: 3866-3876.
    Original languageEnglish
    JournalJournal of Immunology
    Volume182
    Issue number6
    Pages (from-to)3866-3876
    Number of pages11
    ISSN0022-1767
    Publication statusPublished - 2009
    MoE publication typeA1 Journal article-refereed

    Cite this

    Manicone, A. M., Birkland, T. P., Lin, M., Betsuyaku, T., van Rooijen, N., Lohi, J., Keski-Oja, J., Wang, Y., Skerrett, S. J., & Parks, W. C. (2009). Epilysin (MMP-28) restrains early macrophage recruitment in Pseudomonas aeruginosa pneumonia. Journal of Immunology, 182(6), 3866-3876.