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 journalArticle

57 Citations (Scopus)

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 Mmp28-/- 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 Mmp28-/- 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.

Original languageEnglish
Pages (from-to)3866-3876
Number of pages11
JournalJournal of Immunology
Volume182
Issue number6
DOIs
Publication statusPublished - 2009 Mar 15
Externally publishedYes

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Matrix Metalloproteinases
Pseudomonas aeruginosa
Pneumonia
Macrophages
Lung
Neutrophil Infiltration
Bronchoalveolar Lavage Fluid
Alveolar Macrophages
Chemotaxis
Innate Immunity
Leukocytes
Epithelial Cells
Genotype
Phenotype

ASJC Scopus subject areas

  • Immunology
  • Medicine(all)

Cite this

Manicone, A. M., Birkland, T. P., Lin, M., Betsuyaku, T., Van Rooijen, N., Lohi, J., ... Parks, W. C. (2009). Epilysin (MMP-28) restrains early macrophage recruitment in Pseudomonas aeruginosa pneumonia. Journal of Immunology, 182(6), 3866-3876. https://doi.org/10.4049/jimmunol.0713949

Epilysin (MMP-28) restrains early macrophage recruitment in Pseudomonas aeruginosa pneumonia. / Manicone, Anne M.; Birkland, Timothy P.; Lin, Michelle; Betsuyaku, Tomoko; Van Rooijen, Nico; Lohi, Jouko; Keski-Oja, Jorma; Wang, Ying; Skerrett, Shawn J.; Parks, William C.

In: Journal of Immunology, Vol. 182, No. 6, 15.03.2009, p. 3866-3876.

Research output: Contribution to journalArticle

Manicone, AM, Birkland, TP, Lin, M, Betsuyaku, T, Van Rooijen, N, Lohi, J, Keski-Oja, J, Wang, Y, Skerrett, SJ & Parks, WC 2009, 'Epilysin (MMP-28) restrains early macrophage recruitment in Pseudomonas aeruginosa pneumonia', Journal of Immunology, vol. 182, no. 6, pp. 3866-3876. https://doi.org/10.4049/jimmunol.0713949
Manicone AM, Birkland TP, Lin M, Betsuyaku T, Van Rooijen N, Lohi J et al. Epilysin (MMP-28) restrains early macrophage recruitment in Pseudomonas aeruginosa pneumonia. Journal of Immunology. 2009 Mar 15;182(6):3866-3876. https://doi.org/10.4049/jimmunol.0713949
Manicone, Anne M. ; Birkland, Timothy P. ; Lin, Michelle ; Betsuyaku, Tomoko ; Van Rooijen, Nico ; Lohi, Jouko ; Keski-Oja, Jorma ; Wang, Ying ; Skerrett, Shawn J. ; Parks, William C. / Epilysin (MMP-28) restrains early macrophage recruitment in Pseudomonas aeruginosa pneumonia. In: Journal of Immunology. 2009 ; Vol. 182, No. 6. pp. 3866-3876.
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