title: Expression of area-specific M2-macrophage phenotype by recruited rat monocytes in duct-ligation pancreatitis.
abstract: Acute pancreatitis remains a disease of uncertain pathogenesis and no established specific therapy. Previously, we found a predominant increase and active proliferation of macrophages in the inflamed tissues of a rat duct-ligation pancreatitis model. To analyze the origin and possible role of these macrophages, we investigated their in situ cellular kinetics in a rat model of duct-ligation pancreatitis using a recently established method of multicolor immunostaining for macrophage markers and for proliferating cells with ethynyl deoxyuridine. To detect monocyte-derived macrophages, green fluorescent protein-transgenic (GFP(+)) leukocytes were transferred to monocyte-depleted recipients. In the inflamed pancreas, infiltrating macrophages were mainly two phenotypes, CD68(+)CD163(-) round cells and CD68(+)CD163(+) large polygonal cells, both of which showed active proliferation. In the interlobular area, the proportions of CD68(+)CD163(low) and CD68(+)CD163(high) cells increased over time. Most expressed the M2-macrophage markers CD206 and arginase 1. In contrast, in the interacinar area, CD68(+) cells did not upregulate CD163 and CD206, but ~30 % of them expressed the M1 marker nitric oxide synthase 2 on day 4. GFP(+)-recruited cells were primarily CD68(+)CD163(-) monocytes on day 1 and showed phenotypic changes similar to those of the monocyte non-depleted groups. In conclusion, infiltrating macrophages mostly formed two distinct subpopulations in different areas: monocyte-derived macrophages with the M2 phenotype in the interlobular area or non-M2 phenotype in the interacinar area. Involvement of resident macrophages might be minor in this model. These results are the first demonstration of an upregulated M2 phenotype in rat inflammatory monocytes, which may promote tissue repair.
authors: Department of Anatomy (Macro), School of Medicine, Dokkyo Medical University, Mibu, Tochigi, 321-0293, Japan.|Department of General Surgery, Affiliated Wujiang Hospital of Nantong University, Suzhou, Jiangsu, China.
authors: Enqiao
authors: E
authors: Yu
authors: NHO Miyakonojo Medical Center, Miyazaki, Japan.
authors: Mataro
authors: M
authors: Goto
authors: Department of Anatomy (Macro), School of Medicine, Dokkyo Medical University, Mibu, Tochigi, 321-0293, Japan.
authors: Hisashi
authors: H
authors: Ueta
authors: Department of Anatomy (Macro), School of Medicine, Dokkyo Medical University, Mibu, Tochigi, 321-0293, Japan.
authors: Yusuke
authors: Y
authors: Kitazawa
authors: Department of Anatomy (Macro), School of Medicine, Dokkyo Medical University, Mibu, Tochigi, 321-0293, Japan.
authors: Yasushi
authors: Y
authors: Sawanobori
authors: Department of Anatomy (Macro), School of Medicine, Dokkyo Medical University, Mibu, Tochigi, 321-0293, Japan.
authors: Taro
authors: T
authors: Kariya
authors: Department of Anatomy (Macro), School of Medicine, Dokkyo Medical University, Mibu, Tochigi, 321-0293, Japan.
authors: Masaru
authors: M
authors: Sasaki
authors: Department of Anatomy (Macro), School of Medicine, Dokkyo Medical University, Mibu, Tochigi, 321-0293, Japan. kenjiro@dokkyomed.ac.jp.
authors: Kenjiro
authors: K
authors: Matsuno
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D004195:Disease Models, Animal; D007700:Kinetics; D008026:Ligation; D008264:Macrophages / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009000:Monocytes / Q000378:metabolism* / Q000473:pathology; D010195:Pancreatitis / Q000378:metabolism* / Q000473:pathology / Q000601:surgery*; D010641:Phenotype; D051381:Rats; D011917:Rats, Inbred Lew; D017208:Rats, Wistar
chemical_list: D015703:Antigens, CD
keywords: Cellular kinetics; M2 macrophage; Monocyte recruitment; Multicolor immunostaining; Pancreatitis; Proliferation