Abstract
Microfibrillar-associated protein 4 (MFAP4) is a matricellular protein abundant in lungs. Its functions remain largely unknown. However, due to presence of an integrin-binding site and structural similarities to many proteins engaged in innate immune defences, MFAP4 is thought to be an active modulator of immune response and tissue remodeling.
The aim of the current study is to investigate a potential role of MFAP4 in the murine model of allergic asthma.
BALB/c WT and MFAP4-deficient mice were sensitized and subsequently challenged intranasally with ovalbumin (OVA). Immune cell infiltration and cytokine production were measured in bronchoalveolar lavage (BAL) and lung tissue. Lungs were processed for histology and evaluated for signs of inflammation and airway remodeling.
OVA-treated MFAP4 KO mice exhibited significantly lowered cell counts in BAL, corresponding to diminished numbers of infiltrating eosinophils and neutrophils. The production of Th2-related cytokines IL-4, IL-5 and IL-13 was reduced in the airways of MFAP4-deficient animals. Moreover, histological stainings revealed significant differences in lung morphology: more prominent parenchymal inflammation and more pronounced airway remodeling in WT mice, including goblet cell hyperplasia and increased smooth muscle thickness.
Obtained results show that absence of MFAP4 attenuates OVA-induced allergic airway disease. It indicates that MFAP4 may serve as a potential therapeutic target in the treatment for allergic asthma.
- © 2014 ERS