Influence of acid sphingomyelinase deficiency in a murine model of allergen-induced asthma

Introduction: Acid sphingomyelinase (ASM) deficency causes lipid storage diseases, called Niemann-Pick-disease (NPD) type A (neuronopathic) and B (non-neuronopathic). Previous studies demonstrated an association of NPD type B with respiratory failure and lung infections. We investigated the role of ASM deficiency in a murine model of allergic asthma. Method: Male C57BL/6 (WT) and ASM knockout mice (ASM-KO) were intraperitoneally sensitized with ovalbumin (OVA)/Alum (10μg/1.5mg) on days 0, 14 and 21. Repeated aerosol challenges (1% OVA) followed for five weeks on two consecutive days every week. Bronchoalveolar lavage (BAL), serum and lung tissue were taken for cell counts, cytokine measurements, histology slides and calculation of wet/dry-ratio. Precision-cut lung slices (PCLS) were prepared to investigate early asthmatic response (EAR). Results: Edema formation was less in ASM-KO (73.6±7.6%) compared to WT. In addition, sensitized ASM-KO showed significantly higher cell numbers in BAL and lung tissue primarily consisting of neutrophils and enlarged macrophages, whereas numbers of eosinophils were similar. The ratio of eosinophils and neutrophils was characteristic of a typical Th1-pattern. Differences in cytokine and IgE-levels in BAL and serum were not found. OVA stimulation of PCLS from both mouse strains resulted in a weak bronchoconstriction. Conclusion: ASM-KO showed the typical characteristics of NPD, but their allergic inflammation was similar to that of WT mice, except for an increased neutrophil/eosinophil ratio. The major observation was reduced edema formation in ASM-KO mice. We conclude that ASM contributes to allergic edema formation, a key feature of asthma.