PMID- 11340674 OWN - NLM STAT- MEDLINE DCOM- 20010712 LR - 20061115 IS - 1059-910X (Print) IS - 1059-910X (Linking) VI - 53 IP - 4 DP - 2001 May 15 TI - Role of monocyte chemoattractant protein-1 in Propionibacterium acnes-induced pulmonary granulomatosis. PG - 288-97 AB - The inflammatory process in granulomatous disorders such as sarcoidosis is mainly the consequence of delayed hypersensitivity induced by causative antigens. Propionibacterial DNA was isolated recently by PCR from human sarcoidosis tissue. Hence, we developed a model using sensitized rabbits for T cell-mediated pulmonary granulomatosis induced by Propionibacterium acnes (P. acnes) and investigated the role of monocyte chemoattractant protein-1 (MCP-1) in the pathogenesis of the granuloma formation in vivo. Intravenous injection of P. acnes into sensitized rabbits induced massive pulmonary granulomas on day 3. Maximum levels of MCP-1 in sera and bronchoalveolar lavage fluid (BALF) were detected on day 1 and preceded recruitment of monocyte/macrophages and T cells. In BALF, monocyte chemotaxis peaked 1 day after P. acnes challenge, and T cell chemotaxis peaked 3 days after P. acnes challenge. Anti-MCP-1 IgG inhibited monocyte chemotaxis by 80.2% and T cell chemotaxis by 35.7%. Phenotypic analysis of migrating T cells revealed that activated and memory T cells (CD26(+)/CD45RO(+)) but not naive cells were preferentially attracted to BALF. Administration of MCP-1 antiserum in vivo inhibited the development of granulomas in both size 59.9% reduction and number 28.6% reduction, the number of infiltrating leukocytes in BALF, and the expression of adhesion molecules on leukocytes in peripheral blood and BALF. Our data indicate that MCP-1 plays important roles in granuloma formation by attracting and activating specific types of cells in this model. Furthermore, results suggest that the rabbit model resembles human angiocentric granulomatosis and would be useful for investigating the immunopathogenesis of human pulmonary granulomatosis. CI - Copyright 2001 Wiley-Liss, Inc. FAU - Ichiyasu, H AU - Ichiyasu H AD - First Department of Internal Medicine, Kumamoto University School of Medicine, Kumamoto, Japan. FAU - Suga, M AU - Suga M FAU - Iyonaga, K AU - Iyonaga K FAU - Ando, M AU - Ando M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Microsc Res Tech JT - Microscopy research and technique JID - 9203012 RN - 0 (Chemokine CCL2) RN - 0 (Immune Sera) SB - IM MH - Animals MH - Chemokine CCL2/*immunology MH - Disease Models, Animal MH - Gram-Positive Bacterial Infections/*immunology/microbiology MH - Granuloma, Respiratory Tract/*immunology/microbiology MH - Humans MH - Immune Sera MH - Lung Diseases/*immunology/microbiology MH - Propionibacterium acnes/*immunology/pathogenicity MH - Rabbits MH - T-Lymphocytes/immunology/pathology EDAT- 2001/05/08 10:00 MHDA- 2001/07/13 10:01 CRDT- 2001/05/08 10:00 PHST- 2001/05/08 10:00 [pubmed] PHST- 2001/07/13 10:01 [medline] PHST- 2001/05/08 10:00 [entrez] AID - 10.1002/jemt.1095 [pii] AID - 10.1002/jemt.1095 [doi] PST - ppublish SO - Microsc Res Tech. 2001 May 15;53(4):288-97. doi: 10.1002/jemt.1095.