A critical role for monocytes/macrophages during intestinal inflammation-associated lymphangiogenesis

Research output: Contribution to journalArticle

Authors

External Institution(s)

  • Louisiana State University in Shreveport
  • University of Münster
  • LSU Health Sciences Center - Shreveport

Details

Original languageEnglish (US)
Pages (from-to)1326-1345
Number of pages20
JournalInflammatory bowel diseases
Volume22
Issue number6
StatusPublished - Jun 1 2016
Peer-reviewedYes

Abstract

Background: Inflammation-associated lymphangiogenesis (IAL) is frequently observed in inflammatory bowel diseases. IAL is believed to limit inflammation by enhancing fluid and immune cell clearance. Although monocytes/macrophages (MΦ) are known to contribute to intestinal pathology in inflammatory bowel disease, their role in intestinal IAL has never been studied mechanistically. We investigated contributions of monocytes/MΦ to the development of intestinal inflammation and IAL. Methods: Because inflammatory monocytes express CC chemokine receptor 2 (CCR2), we used CCR2 diphtheria toxin receptor transgenic (CCR2.DTR) mice, in which monocytes can be depleted by diphtheria toxin injection, and CCR2 -/- mice, which have reduced circulating monocytes. Acute or chronic colitis was induced by dextran sodium sulfate or adoptive transfer of CD4 + CD45RB high T cells, respectively. Intestinal inflammation was assessed by flow cytometry, immunofluorescence, disease activity, and histopathology, whereas IAL was assessed by lymphatic vessel morphology and density. Results: We demonstrated that intestinal MΦ expressed vascular endothelial growth factor-C/D. In acute colitis, monocyte-depleted mice were protected from intestinal injury and showed reduced IAL, which was reversed after transfer of wild-type monocytes into CCR2 -/- mice. In chronic colitis, CCR2 deficiency did not attenuate inflammation but reduced IAL. Conclusions: We propose a dual role of MΦ in (1) promoting acute inflammation and (2) contributing to IAL. Our data suggest that intestinal inflammation and IAL could occur independently, because IAL was reduced in the absence of monocytes/MΦ, even when inflammation was present. Future inflammatory bowel disease therapies might exploit promotion of IAL and suppression of MΦ independently, to restore lymphatic clearance and reduce inflammation.

    Research areas

  • CCR2, VEGF-C/D, animal models, colitis, lymphangiogenesis, macrophages

Citation formats

APA

Becker, F., Kurmaeva, E., Gavins, F. N. E., Stevenson, E. V., Navratil, A. R., Jin, L., ... Ostanin, D. V. (2016). A critical role for monocytes/macrophages during intestinal inflammation-associated lymphangiogenesis. Inflammatory bowel diseases, 22(6), 1326-1345. https://doi.org/10.1097/MIB.0000000000000731

Harvard

Becker, F, Kurmaeva, E, Gavins, FNE, Stevenson, EV, Navratil, AR, Jin, L, Tsunoda, I, Orr, AW, Alexander, JS & Ostanin, DV 2016, 'A critical role for monocytes/macrophages during intestinal inflammation-associated lymphangiogenesis', Inflammatory bowel diseases, vol. 22, no. 6, pp. 1326-1345. https://doi.org/10.1097/MIB.0000000000000731