Expression of Macrophage Inflammatory Protein-3 /CCL19 in Pulmonary Sarcoidosis

In this study, messenger RNA (mRNA) expression for novel T described using bioinformatics (5), including the leukotac-lymphocyte chemoattractants, leukotactin-1, macrophage inflam-tin-1 (Lkn-1)/CC chemokine ligand (CCL) 15/hemofiltrate CC matory protein (MIP)-3␣ and MIP-3␤ was investigated in bronchoal-chemokine-2 (6), macrophage inflammatory protein (MIP)-3␣/ veolar lavage fluid (BALF) cells from patients with sarcoidosis, a T CCL20/liver and activation-regulated chemokine (7), and cell–mediated disease with typical CD4ϩ lymphocyte alveolitis. Of MIP-3␤/CCL19/Epstein-Barr virus–induced molecule 1 ligand these three chemokines, only MIP-3␤ mRNA was upregulated inThe chemokine MIP-3␤ is expressed especially in lymphoid macologic regulation, and association with disease clinical course tissues, whereas production of MIP-3␣ is found also in periph-were explored. MIP-3␤ protein concentrations were elevated in eral blood leukocytes and several fetal tissues (7, 8). Expres-BALF from sarcoid patients compared with control subjects (p ϭ sion of Lkn-1 is observed in the liver, intestine, and lung 0.001) and in patients with chest X-ray stage II chemokine protein leukocytes (9). The gene encoding chemokine MIP-3␤ maps levels were increased compared with stage I (p ϭ 0.003). MIP-3␤ on human chromosome 9, whereas most other CC chemokine protein was associated predominantly with alveolar macrophages genes (including MIP-3␣ and Lkn-1) are clustered on chro-and correlated with BALF lymphocytes and T cell subsets. mRNA mosome 17 (8). Although there are significant differences in increased in sarcoidosis and correlated with MIP-3␤ protein levels. transcripts for all three chemokines have been previously MIP-3␤ mRNA and protein expression in BALF cells was suppressed by dexamethasone and cyclosporine A in vitro. In conclusion, MIP-found in samples of human lung tissue (7, 9, 10).The chemokine MIP-3␤ is chemoattractant for T and B ated with disease progression, and is downregulated by drugs used lymphocytes (11, 12), dendritic cells (13), macrophage pro-for sarcoidosis treatment. This novel chemokine, therefore, repre-genitor cells (14), and natural killer cells (15). It might, there-sents a candidate for studies of sarcoidosis pathobiologic mecha-fore, play an important role in the trafficking of T cells in nisms. the thymus and migration of T and B cells to secondary lymphoid organs (12, 16). Furthermore, MIP-3␤ has beenrecently shown to mediate rapid adhesion of naive CD4ϩ T methasone; cyclosporine A lymphocytes to activated endothelial cells supporting the role of this chemokine in regulation of lymphocyte homing (17). Sarcoidosis is a multiorgan granulomatous disorder most fre-MIP-3␤ acts through CC chemokine receptor 7 (CCR7) (8). quently affecting the lung that results from the accumulation The chemokines Lkn-1 …