Mouse monocyte-derived chemokine is involved in airway hyperreactivity andlung inflammation

The cloning, expression, and function of the murine (m) homologue of human (h) monocyte-derived chemokine (MDC) is reported here. Like hMDC, mMDC is a ble to elicit the chemotactic migration in vitro of activated lymphocytes a nd monocytes, Among activated lymphocytes, Th2 cells were induced to migrat e most efficiently, mMDC mRNA and protein expression is modulated during th e course of an allergic reaction in the lung. Neutralization of mMDC with s pecific Abs in a model of lung inflammation resulted in prevention of airwa y hyperreactivity and significant reduction of eosinophils in the lung inte rstitium but not in the airway lumen. These data suggest that mMDC is essen tial in the transit/retention of leukocytes in the lung tissue rather than in their extravasation from the blood vessel or during their transepithelia l migration into the airways. These results also highlight the relevance of factors, such as mMDC, that regulate the migration and accumulation of leu kocytes within the tissue during the development of the key physiological e ndpoint of asthma, airway hyperreactivity.