Expression of area-specific M2-macrophage phenotype by recruited rat monocytes in duct-ligation pancreatitisReport as inadecuate

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Histochemistry and Cell Biology

, Volume 145, Issue 6, pp 659–673

First Online: 09 February 2016Accepted: 06 January 2016DOI: 10.1007-s00418-016-1406-y

Cite this article as: Yu, E., Goto, M., Ueta, H. et al. Histochem Cell Biol 2016 145: 659. doi:10.1007-s00418-016-1406-y


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, CD68CD163 round cells and CD68CD163 large polygonal cells, both of which showed active proliferation. In the interlobular area, the proportions of CD68CD163 and CD68CD163 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 CD68CD163 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.

KeywordsPancreatitis Multicolor immunostaining Cellular kinetics Proliferation Monocyte recruitment M2 macrophage Mataro Goto and Hisashi Ueta have contributed equally to this work.

Electronic supplementary materialThe online version of this article doi:10.1007-s00418-016-1406-y contains supplementary material, which is available to authorized users.

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Author: Enqiao Yu - Mataro Goto - Hisashi Ueta - Yusuke Kitazawa - Yasushi Sawanobori - Taro Kariya - Masaru Sasaki - Kenjiro Mats


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