Blockade of secondary lymphoid tissue chemokine exacerbates Propionibacterium acnes-induced acute lung inflammation

Chemokine-chemokine receptor interaction plays an essential role in leukocy te/dendritic cell(DC) trafficking in inflammation and immune responses. We investigated the pathophysiological roles of secondary lymphoid tissue chem okine (SLC; CCL21) and macrophage inflammatory protein-2 (MIP-2) in the dev elopment of acute pulmonary inflammation induced by an intratracheal inject ion of Propionibacterium acnes in mice. Immunohistochemical studies reveale d that SLC was constitutively expressed in the peribronchial areas and peri vascular lymphatics in normal mice, MIP-2-positive cells were observed in a lveolar spaces in mice challenged with P, acnes, Both neutralization Abs ag ainst MIP-2 and CXC chemokine receptor 2 alleviated the P, acnes-induced pu lmonary inflammation when injected before P, acnes Ag challenge. On the oth er hand, polyclonal anti-SLC Abs (pAbs) exacerbated the pulmonary inflammat ion. The numbers of mature DCs (MHC class II+, CD11c(+), and CD86(+)) as we ll as macrophages and neutrophils in the P, acnes Ag-challenged lungs were increased, whereas the number of CD4(+) T cells, including memory T cells, was decreased. The numbers of mature and proliferating CD4(+) T cells (brom odeoxyuridine(+)CD4(+)) in regional lymph nodes were decreased in mice inje cted with anti-SLC pAbs compared with those in mire treated with control Ab s, An in vitro proliferation assay confirmed the impairment of the Ag-speci fic T cell response in regional lymph nodes of mice treated with anti-SLC p Abs, These results indicate for the first time a regulatory role for SLC-re cruited mature DCs in bridging an acute inflammatory response (innate immun ity) and acquired immunity in the lung.