Expression of Macrophage Inflammatory Protein (MIP)-3β/CCL19 in pulmonary sarcoidosis

In this study, mRNA expression for novel T-lymphocyte chemoattractants, Leukotactin-1, Macrophage inflammatory protein (MIP)-3α and MIP-3β, was investigated in bronchoalveolar lavage fluid (BALF) cells from patients with sarcoidosis, a T-cell-mediated disease with typical CD4+ lymphocyte alveolitis. Of these three chemokines, only MIP-3β mRNA was upregulated in sarcoidosis and, therefore, protein levels of this chemokine, its pharmacological regulation and association with disease clinical course were explored. MIP-3β protein concentrations were elevated in BALF from sarcoid patients compared to control subjects (p=0.001), and in patients with CXR-Stage-II chemokine protein levels were increased compared to Stage-I (p=0.003). MIP-3β protein was associated predominantly with alveolar macrophages and correlated with BALF lymphocytes and T-cell subsets. mRNA expression for the MIP-3β receptor, CC chemokine receptor (CCR)7, was increased in sarcoidosis and correlated with MIP-3β protein levels. MIP-3β mRNA and protein expression in BALF cells was suppressed by Dexamethasone and Cyclosporine A in vitro. In conclusion, MIP-3β is implicated in T-lymphocyte recruitment in sarcoidosis, is associated with disease progression and downregulated by drugs used for sarcoidosis treatment. This novel chemokine, therefore, represents a candidate for studies of sarcoidosis pathobiological mechanisms. The number of words: 183