Abstract
Gap junction channels are sites of cytoplasmic communication between contacting cells. In vertebrates, they consist of protein subunits denoted connexins (Cxs) which are encoded by a gene family. According to their Cx composition, gap junction channels show different gating and permeability properties that define which ions and small molecules permeate them. Differences in Cx primary sequences suggest that channels composed of different Cxs are regulated differentially by intracellular pathways under specific physiological conditions. Functional roles of gap junction channels could be defined by the relative importance of permeant substances, resulting in coordination of electrical and/or metabolic cellular responses. Cells of the native and specific immune systems establish transient homo- and heterocellular contacts at various steps of the immune response. Morphological and functional studies reported during the last three decades have revealed that many intercellular contacts between cells in the immune response present gap junctions or "gap junction-like" structures. Partial characterization of the molecular composition of some of these plasma membrane structures and regulatory mechanisms that control them have been published recently. Studies designed to elucidate their physiological roles suggest that they might permit coordination of cellular events which favor the effective and timely response of the immune system.
Highlights
Numerous reports have described different mechanisms for intercellular communication between members of the immune system, including cell adhesion molecules, membrane molecules that act as ligand-receptors [1] and soluble molecules secreted into the extracellular milieu which act as paracrine and autocrine signals [2]
Gap junctions in the bone marrow and secondary lymphoid organs. Both in vivo [29] and in vitro [30,31] studies have demonstrated that bone marrow stromal cells form gap junctions
P388D1 or J744 macrophages cocultured with epithelial cell lines show homocellular dye coupling, as well as heterocellular dye coupling with epithelial cell lines [25], suggesting that soluble factors present in the co-culture induce macrophages to form gap junctions
Summary
Numerous reports have described different mechanisms for intercellular communication between members of the immune system, including cell adhesion molecules, membrane molecules that act as ligand-receptors [1] and soluble molecules secreted into the extracellular milieu which act as paracrine and autocrine signals [2]. Two reviews have described gap junction communication between cells of the immune system [3,4]. It has been shown that gap junction channels and hemichannels can result from the interaction of two different Cxs [5]. Numerous reports have shown that gap junction communication can be regulated at various cellular levels, including mRNA transcription, mRNA stability and channel gating [5]. The homocellular gap junctional communication at cell-cell contacts between other members of the immune system, such as macrophages [10,11], follicular dendritic cells [12], thymic epithelial cells [13], polymorphonuclear (PMN) cells [14,15] and microglia [16] has been reported. Heterocellular gap junctional communication between lymphocytes and endothelial cells [23], thymocytes and thymic epithelial cells [13], macrophages and epithelial cells [24,25,26], mastocytoma cells and lymphocytes [27] and follicular dendritic cells and B-cells [28] has been reported
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