Inhibition of CCL1-CCR8 interaction prevents aggregation of macrophages and development of peritoneal adhesions

Akiyoshi Hoshino, Yuki I. Kawamura, Masato Yasuhara, Noriko Toyama-Sorimachi, Kenji Yamamoto, Akihiro Matsukawa, Sergio A. Lira, Taeko Dohi

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48 Citations (Scopus)

Abstract

Peritoneal adhesions are a significant complication of surgery and visceral inflammation; however, the mechanism has not been fully elucidated. The aim of this study was to clarify the mechanism of peritoneal adhesions by focusing on the cell trafficking and immune system in the peritoneal cavity. We investigated the specific recruitment of peritoneal macrophages (PMφ) and their expression of chemokine receptors in murine models of postoperative and postinflammatory peritoneal adhesions. PMφ aggregated at the site of injured peritoneum in these murine models of peritoneal adhesions. The chemokine receptor CCR8 was up-regulated in the aggregating PMφ when compared with naive PMφ. The up-regulation of CCR8 was also observed in PMφ, but not in bone marrow-derived Mφ, treated with inflammatory stimulants including bacterial components and cytokines. Importantly, CCL1, the ligand for CCR8, a product of both PMφ and peritoneal mesothelial cells (PMCs) following inflammatory stimulation, was a potent enhancer of CCR8 expression. Cell aggregation involving PMφ and PMCs was induced in vitro in the presence of CCL1. CCL1 also up-regulated mRNA levels of plasminogen activator inhibitor-1 in both PMφ and PMCs. CCR8 gene-deficient mice or mice treated with anti-CCL1-neutralizing Ab exhibited significantly reduced postoperational peritoneal adhesion. Our study now establishes a unique autocrine activation system in PMφ and the mechanism for recruitment of PMφ together with PMCs via CCL1/CCR8, as immune responses of peritoneal cavity, which triggers peritoneal adhesions.

Original languageEnglish
Pages (from-to)5296-5304
Number of pages9
JournalJournal of Immunology
Volume178
Issue number8
DOIs
Publication statusPublished - Apr 15 2007

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Hoshino, A., Kawamura, Y. I., Yasuhara, M., Toyama-Sorimachi, N., Yamamoto, K., Matsukawa, A., Lira, S. A., & Dohi, T. (2007). Inhibition of CCL1-CCR8 interaction prevents aggregation of macrophages and development of peritoneal adhesions. Journal of Immunology, 178(8), 5296-5304. https://doi.org/10.4049/jimmunol.178.8.5296