Advertisement

Lung

, Volume 197, Issue 6, pp 819–823 | Cite as

Deletion of LysM in LysMCre Recombinase Homozygous Mice is Non-contributory in LPS-Induced Acute Lung Injury

  • Ke-Qin Gong
  • Charles Frevert
  • Anne M. ManiconeEmail author
ACUTE LUNG INJURY

Abstract

Lysozyme is an important component of the innate immune system and has roles in peptidoglycan cleavage of gram-positive organisms. Myeloid cells highly express the isoform, lysozyme M, and its promoter has been used to direct Cre recombinase expression to target deletion of floxed genes in myeloid cells. However, generation of the LysMCre mouse effectively disrupts the LysM gene, and mice homozygous for the Cre allele lack the LysM gene product. To test the contribution of LysM in sterile acute lung injury, we generated LysMCre mice homozygous for the Cre allele (+/+) or wild-type allele (−/−). These mice were challenged with LPS delivered via oropharygneal aspiration. Mice were monitored and weighed daily, and BAL cell counts, differential, protein, and cytokine levels were assessed at days 2 and 4. LysMCre+/+ and LysMCre−/− had similar weight loss and recovery, and similar inflammatory responses to LPS at days 2 and 4. These findings indicate that loss of LysM and expression of Cre recombinase are non-contributory in sterile acute lung injury.

Keywords

Murine Lysozyme LysMCre ALI Acute lung injury 

Notes

Funding

This work was supported by R01 HL116514 (AMM), R01 HL144656 (CF), and P30-ES-007033-19-6363 (AMM, CF).

Compliance with Ethical Standards

Conflict of interest

All authors declare that they have no conflict of interest.

References

  1. 1.
    Cross M, Mangelsdorf I, Wedel A, Renkawitz R (1988) Mouse lysozyme M gene: isolation, characterization, and expression studies. Proc Natl Acad Sci USA 85:6232–6236CrossRefGoogle Scholar
  2. 2.
    Ishiguro K, Yoshie N, Sakurai M, Inoue Y (1992) A 1H NMR study of a fragment of partially n-acetylated chitin produced by lysozyme degradation. Carbohydr Res 237:333–338CrossRefGoogle Scholar
  3. 3.
    Pangburn SH, Trescony PV, Heller J (1982) Lysozyme degradation of partially deacetylated chitin, its films and hydrogels. Biomaterials 3:105–108CrossRefGoogle Scholar
  4. 4.
    Ibrahim HR, Matsuzaki T, Aoki T (2001) Genetic evidence that antibacterial activity of lysozyme is independent of its catalytic function. FEBS Lett 506:27–32CrossRefGoogle Scholar
  5. 5.
    LeMarbre P, Rinehart JJ, Kay NE, Vesella R, Jacob HS (1981) Lysozyme enhances monocyte-mediated tumoricidal activity: a potential amplifying mechanism of tumor killing. Blood 58:994–999CrossRefGoogle Scholar
  6. 6.
    Akinbi HT, Epaud R, Bhatt H, Weaver TE (2000) Bacterial killing is enhanced by expression of lysozyme in the lungs of transgenic mice. J Immunol 165:5760–5766CrossRefGoogle Scholar
  7. 7.
    Markart P, Korfhagen TR, Weaver TE, Akinbi HT (2004) Mouse lysozyme M is important in pulmonary host defense against Klebsiella pneumoniae infection. Am J Respir Crit Care Med 169:454–458CrossRefGoogle Scholar
  8. 8.
    Clausen BE, Burkhardt C, Reith W, Renkawitz R, Forster I (1999) Conditional gene targeting in macrophages and granulocytes using LysMcre mice. Transg Res 8:265–277CrossRefGoogle Scholar
  9. 9.
    Abram CL, Roberge GL, Hu Y, Lowell CA (2014) Comparative analysis of the efficiency and specificity of myeloid-Cre deleting strains using ROSA-EYFP reporter mice. J Immunol Methods 408:89–100CrossRefGoogle Scholar
  10. 10.
    McCubbrey AL, Allison KC, Lee-Sherick AB, Jakubzick CV, Janssen WJ (2017) Promoter specificity and efficacy in conditional and inducible transgenic targeting of lung macrophages. Front Immunol 8:1618CrossRefGoogle Scholar
  11. 11.
    Jiang Z, Chen Z, Li L, Zhou W, Zhu L (2017) Lack of SOCS3 increases LPS-induced murine acute lung injury through modulation of Ly6C(+) macrophages. Respir Res 18:217CrossRefGoogle Scholar
  12. 12.
    Xia H, Ren X, Bolte CS, Ustiyan V, Zhang Y, Shah TA, Kalin TV, Whitsett JA, Kalinichenko VV (2015) Foxm1 regulates resolution of hyperoxic lung injury in newborns. Am J Respir Cell Mol Biol 52:611–621CrossRefGoogle Scholar
  13. 13.
    Eddy WE, Gong KQ, Bell B, Parks WC, Ziegler SF, Manicone AM (2017) Stat5 is required for CD103(+) dendritic cell and alveolar macrophage development and protection from lung injury. J Immunol 198:4813–4822CrossRefGoogle Scholar
  14. 14.
    Manicone AM, Gharib SA, Gong KQ, Eddy WE, Long ME, Frevert CW, Altemeier WA, Parks WC, Houghton AM (2017) Matrix metalloproteinase-28 is a key contributor to emphysema pathogenesis. Am J Pathol 187:1288–1300CrossRefGoogle Scholar
  15. 15.
    Kilkenny C, Browne W, Cuthill IC, Emerson M, Altman DG, Group NCRRGW (2010) Animal research: reporting in vivo experiments: the ARRIVE guidelines. Br J Pharmacol 160:1577–1579CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Division of Pulmonary and Critical Care Medicine, Center for Lung BiologyUniversity of WashingtonSeattleUSA
  2. 2.Department of Comparative Medicine, Center for Lung BiologyUniversity of WashingtonSeattleUSA

Personalised recommendations