Muscularis macrophages establish cell-to-cell contacts with telocytes/PDGFRα-positive cells and smooth muscle cells in the human and mouse gastrointestinal tract

Neurogastroenterol Motil. 2021 Mar;33(3):e13993. doi: 10.1111/nmo.13993. Epub 2020 Oct 5.

Abstract

Background and aim: Muscularis macrophages (MMs) not only mediate the innate immunity, but also functionally interact with cells important for gastrointestinal motility. The aim of this study was to determine the spatial relationship and types of contacts between the MMs and neighboring cells in the muscularis propria of human and mouse stomach, small intestine, and large intestine.

Methods: The distribution and morphology of MMs and their contacts with other cells were investigated by immunohistochemistry and transmission electron microscopy.

Key results: Immunohistochemistry showed variable shape and number of MMs according to their location in different portions of the muscle coat. By double labeling, a close association between MMs and neighboring cells, that is, neurons, smooth muscle cells, interstitial cells of Cajal (ICCs), telocytes (TCs)/PDGFRα-positive cells, was seen. Electron microscopy demonstrated that in the muscle layers of both animal species, MMs have similar ultrastructural features and have specialized cell-to-cell contacts with smooth muscle cells and TCs/PDGFRα-positive cells but not with ICCs and enteric neurons.

Conclusion & inferences: This study describes varying patterns of distribution of MMs between different regions of the gut, and reports the presence of distinct and extended cell-to-cell contacts between MMs and smooth muscle cells and between MMs and TCs/PDGFRα-positive cells. In contrast, MMs, although close to ICCs and nerve elements, did not make contact with them. These findings indicate specialized and variable roles for MMs in the modulation of gastrointestinal motility whose significance should be more closely investigated in normal and pathological conditions.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Communication
  • Enteric Nervous System
  • Female
  • Gastric Mucosa / cytology*
  • Gastric Mucosa / metabolism
  • Gastric Mucosa / ultrastructure
  • Humans
  • Intercellular Junctions / ultrastructure*
  • Interstitial Cells of Cajal / cytology
  • Interstitial Cells of Cajal / metabolism
  • Interstitial Cells of Cajal / ultrastructure
  • Intestinal Mucosa / cytology*
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / ultrastructure
  • Macrophages / cytology*
  • Macrophages / metabolism
  • Macrophages / ultrastructure
  • Male
  • Mice
  • Microscopy, Electron, Transmission
  • Middle Aged
  • Myocytes, Smooth Muscle / cytology*
  • Myocytes, Smooth Muscle / metabolism
  • Myocytes, Smooth Muscle / ultrastructure
  • Receptor, Platelet-Derived Growth Factor alpha / metabolism
  • Telocytes / cytology*
  • Telocytes / metabolism
  • Telocytes / ultrastructure

Substances

  • Receptor, Platelet-Derived Growth Factor alpha