Pneumologie 2014; 68 - A20
DOI: 10.1055/s-0033-1363113

The antimicrobial peptide cathelicidin is required for lung repair

C Herr 1, 2, S AlAlwani 2, AÖ Yildirim 3, C Beißwenger 1, R Bals 1, 2
  • 1Universität des Saarlandes, Innere Medizin V, Pneumologie, Allergologie und Beatmungsmedizin, Homburg
  • 2Klinische Forschergruppe „Chronische Atemwegserkrankungen“, Fachbereiche Medizin, Philipps-Universität Marburg, Marburg
  • 3Klinik für Innere Medizin mit Schwerpunkt Pneumologie, Fachbereich Medizin, Philipps-Universität Marburg

Rationale: The antimicrobial peptide cathelicidin is expressed in cells of the innate immune system like macrophages, neutrophils and bronchial epithelial cells. Humans and mice express only one cathelicidin which is termed hCAP-18/LL-37 in humans and CRAMP in mice. Besides its antimicrobial properties cathelicidin has been shown to regulate tumor growth and angiogenesis in vivo, and wound repair in vitro. To investigate the contribution of CRAMP to wound repair in vivo we used CRAMP-ko mice in two lung damage models. We can show that CRAMP contributes to the regeneration of airway epithelial cells after naphthalene induced lung injury and increases the repair of lung tissue after elastase damage.

Methods: To show the contribution of CRAMP to lung repair we used two established lung damage models. CRAMP-ko mice and the corresponding wt controls were treated with naphthalene or corn oil i.p.. The lungs were removed 1 d, 5 d, and 15 d after the treatment and analyzed for CC10-positive cells. In the elastase model the animals received 2,25 mg/kg bodyweight elastase via the endotracheal route. After 30 d we analyzed the lungs by lung-function with a FlexiVent system and by stereology. The activity of MMP9 in broncho-alveolar lavage fluid (BALF) was quantified and the expression of proteins that are involved in tissue repair was analyzed by RT-PCR.

Results: CRAMP-ko showed a significantly delayed regeneration of CC10 positive cells after naphthalene treatment. Elastase treated CRAMP-ko mice had increased cell numbers in BALF after 1 d, 3 d, and 30 d. The lung functional and stereological measurements showed less elastance and resistance and a higher mean linear intercept than the elastase treated wt mice. CRAMP-ko mice expressed more MMP9 after elastase treatment and had a higher activity of MMP9 in the BALF after elastase treatment. The expression of FIZZ1 (RELM-α), a marker for macrophages with wound healing properties, was significantly upregulated in the lungs of elastase treated CRAMP-ko mice.

Conclusion: Our results show that the antimicrobial peptide cathelicidin plays an important role during the regeneration of elastase and naphthalene induced lung injury in mice. We can show that CRAMP-ko mice develop more emphysema than the corresponding wt controls. Since cathelicidin is also expressed in myeloid and epithelial cells of human lungs, this mechanism may be important for the progression and treatment of COPD.