Adhesion and gap junctional communication between macrophages (Mφ) and intestinal epithelial cells (IEC)
Inflammatory Bowel Diseases
In intestinal inflammation, submucosal inflammatory cell infiltrates are found juxtaposed to IEC basolateral membranes. Using a coculture system and flow cytometric analysis, we found that calcein-labeled murine Mφ adhered and transferred dye to IEC monolayers of Mode-K (murine) and IEC6 (rat) cells, but not CMT-93 (murine). Adhesion was partially dependent on Mφ β2 integrin function but the IEC β2 ligand was not ICAM-1. Calcein dye transfer was bi-directional and strictly adhesion dependent, as is characteristic of gap junctional coupling. While Mφ did not adhere to CMT-93 monolayers, CMT-93 did adhere to Mφ and Mode-K monolayers, suggesting that CMT-93 adhesion molecule expression was restricted to basolateral membranes. We detected both homo- and heterocellular dye transfer in cocultures of IEC and/or Mφ. Both adhesion and dye transfer were inhibited with heptanol. Furthermore, propagation of calcium waves between IEC, and between IEC and adherent Mφ indicated communication via gap junctions. Electron micrographs showed close apposition of IEC and Mφ membranes, typical of gap junction formation. These data indicate that IEC and Mφ can interact through gap junctions and suggest a means by which inflammatory cells may regulate IEC function.