Macrophages influence gap junctional intercellular communication between smooth muscle cells in a co-culture model

The present study demonstrates for the first time that cells cultured on pore membrane inserts (macrophages) modulate gap junctional intercellular communication (GJIC) between a second cell type (smooth muscle cells (SMC)) co-cultured in Transwell-COL cell culture chambers. Unstimulated J774A.1 murine macrophages reduced GJIC between human SMC. Stimulation of J774A.1 cells by lipopolysaccharide (LPS) or interferon-γ abrogated this modulation of GJIC. Unstimulated human monocyte-macrophages did not affect GJIC between human SMC. Upon stimulation of these monocyte-macrophages with LPS, a substantial increase in GJIC between co-cultured SMC was observed. Thus, activation of macrophages alters their interaction with co-cultured SMC. Since these results were obtained in an indirect co-culture system in which direct cell-cell contact is prevented, it is hypothesized that soluble factors released by macrophages may be involved in this modulation of GJIC between SMC. The possible nature of the responsible soluble factors is discussed in the context of atherosclerosis.