Methods: Ovalbumin (OVA)-induced allergic asthma murine model was established with wild type and ALCAM knockout mice. Airway hyperresponsiveness, inflammatory cell count, histology, cytokine level, and serum antibodies were measured and analysed. To investigate the therapeutic effect of ALCAM, either control or ALCAM antibody was administrated intranasally 30 min before challenging OVA or PBS. T cell-DC co-culture was conducted with CD3+CD4+ T cell and irradiated CD11b+CD11c+ DC from splenocytes of OVA sensitized mice, and proliferation was measured with CCK-8. The Level of ALCAM in sputum and serum of asthma patients and control subjects were quantified with ELISA.
Result: The level of ALCAM was increased in the bronchial alveolar lavage fluid (BALF) and serum of OVA treated group. ALCAM knockout mice showed diminished inflammatory response compare to the wild type mice. And, in the co-culture experiment, T cells co-cultured with ALCAM‾/‾ DC showed lower proliferation rate than the T cell co-cultured with ALCAM+/+ DC. Human data also showed higher ALCAM level in the sputum and serum of asthma patients than control subjects.
Conclusion: ALCAM has critical role in the pathgenesis of OVA-induced allergic asthma in murine model having an effect on T cell activation and proliferation. Furthermore ALCAM could be used as a biomarker and therapeutic target for asthmatic disease.