Pneumologie 2012; 66 - P2_009
DOI: 10.1055/s-0032-1329810

Surfactant protein D and it role on inflammatory responses in the cigarette-induced COPD model

H Wulf-Johansson 1, C Støttrup 1, S Hansen 2, A Schlosser 1, C Stevenson 3, U Holmskov 1, GL Sorensen 1
  • 1Cardiovascular and Renal Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark
  • 2Cancer and Inflammation Research, University of Southern Denmark, Odense, Denmark
  • 3Inflammation Discovery Translational Area, Hoffmann-La Roche, Nutley, USA

Background: Surfactant protein D (SP-D) is a calcium-dependent carbohydrate molecule mainly produced by Type II pneumocytes and Clara cells in the lung. SP-D is involved in the innate immune system acting as an opsonin on the mucosal surfaces facilitating clearance of bacterial, viral, fungal or allergen challenge or other particulate material. Systemic SP-D variations, as well as, genetic variations have been associated to lung function in chronic obstructive pulmonary disease (COPD). SP-D deficient mice spontaneously develop an emphysema-like pathology with excessive inflammation. In the present study, the effect of SP-D on inflammatory responses and airway resistance was evaluated using the cigarette smoke-induced COPD model in SP-D deficient mice.

Hypothesis: We hypothesize that SP-D plays a regulatory role in inflammation, and genetic ablation of SP-D leads to increased lung inflammation and lung destruction in response to CS exposure in mice.

Methods: C57BL/6N SP-D wildtype and SP-D KO littermate male mice where exposed to CS for 2×50min/5 days/12 weeks and control mice received room air. Inflammatory cell counts were performed in bronchoalveolar lavage (BAL) and lung mechanics were performed with a computer-controlled respirator (FlexiVent, Scireq Inc) using the snapshot perturbation.

Results: Total cell count in BAL fluid showed significant induction with both gene deficiency and cigarette exposure. Numbers of macrophages in BAL fluid increased significantly with both CS and SP-D deficiency and increased number of multinucleated macrophages were observed.. An increased of lymphocytes, neutrophils and eosinophils were observed after CS exposure. Pulmonary function analysis showed that respiratory resistance was increased in mice exposed to CS, but not affected significantly by gene-deficiency.

Conclusion: The findings indicate that SP-D primarily plays dampening role in the cigarette-smoke induced inflammatory responses of the lung. The perspective of the study will now be to investigate how SP-D affects macrophage phagocytosis of particles from cigarette smoke.