Blockade of secondary lymphoid tissue chemokine exacerbates Propionibacterium acnes-induced acute lung inflammation.
Chemokine-chemokine receptor interaction plays an essential role in leukocyte/dendritic cell (DC) trafficking in inflammation and immune responses. We investigated the pathophysiological roles of secondary lymphoid tissue chemokine (SLC; CCL21) and macrophage inflammatory protein-2 (MIP-2) in the development of acute pulmonary inflammation induced by an intratracheal injection of Propionibacterium acnes in mice. Immunohistochemical studies revealed that SLC was constitutively expressed in the peribronchial areas and perivascular lymphatics in normal mice. MIP-2-positive cells were observed in alveolar spaces in mice challenged with P. acnes. Both neutralization Abs against MIP-2 and CXC chemokine receptor 2 alleviated the P. acnes-induced pulmonary inflammation when injected before P. acnes Ag challenge. On the other hand, polyclonal anti-SLC Abs (pAbs) exacerbated the pulmonary inflammation. The numbers of mature DCs (MHC class II +, CD11c+, and CD86+) as well 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 (bromodeoxyuridine(+)CD4+) in regional lymph nodes were decreased in mice injected with anti-SLC pAbs compared with those in mice treated with control Abs. An in vitro proliferation assay confirmed the impairment of the Ag-specific T cell response in regional lymph nodes of mice treated with anti-SLC pAbs. These results indicate for the first time a regulatory role for SLC-recruited mature DCs in bridging an acute inflammatory response (innate immunity) and acquired immunity in the lung.
Itakura
M
M
Department of Molecular Preventive Medicine and Core Research for Evolutional Science and Technology, University of Tokyo School of Medicine, Bunkyoku, Tokyo, Japan.
Tokuda
A
A
Kimura
H
H
Nagai
S
S
Yoneyama
H
H
Onai
N
N
Ishikawa
S
S
Kuriyama
T
T
Matsushima
K
K
D000208:Acute Disease; D000818:Animals; D000907:Antibodies, Bacterial / Q000008:administration & dosage; D000942:Antigens, Bacterial / Q000008:administration & dosage / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000382:microbiology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D054421:Chemokine CCL21; D054426:Chemokine CXCL2; D018925:Chemokines / Q000032:analysis / Q000276:immunology; D019742:Chemokines, CC / Q000032:analysis / Q000037:antagonists & inhibitors* / Q000276:immunology; D002634:Chemotaxis, Leukocyte; D003713:Dendritic Cells / Q000276:immunology / Q000473:pathology; D005260:Female; D016908:Gram-Positive Bacterial Infections / Q000276:immunology* / Q000473:pathology*; D007106:Immune Sera / Q000008:administration & dosage; D007150:Immunohistochemistry; D007156:Immunologic Memory; D007249:Inflammation / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D007275:Injections, Intravenous; D007442:Intubation, Intratracheal; D007958:Leukocyte Count; D008168:Lung / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D008198:Lymph Nodes / Q000737:chemistry / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation; D008221:Lymphoid Tissue / Q000276:immunology* / Q000382:microbiology; D016676:Macrophages, Alveolar / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000276:immunology / Q000473:pathology; D011425:Propionibacterium acnes / Q000276:immunology*; D011817:Rabbits
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; C515479:Ccl21c protein, mouse; D054421:Chemokine CCL21; D054426:Chemokine CXCL2; D018925:Chemokines; D019742:Chemokines, CC; C404915:Cxcl2 protein, mouse; D007106:Immune Sera