The connective connection:: interstitial cells of Cajal (ICC) and ICC-like cells establish synapses with immunoreactive cells.: Electron microscope study in situ.

We present transmission electron microscope (TEM) evidence that ICC and ICC-like cells frequently establish close contacts (synapses) with several types of immunoreactive cells (IRC): lymphocytes, plasma cells, eosinophils, basophils, macrophages and mast cells. Such synapses were found in various organs: human mammary gland and myometrium, as well as rat stomach, gut, bladder and uterus. Specimens were observed by conventional TEM on ultrathin sections. Based on morphometric analyses and computer-aided 3-D reconstructions from serial sections, we propose an operational definition of ICC-IRC synapses: cell-to-cell close contacts where the two cells are separated by only similar to 15nm, equivalent to twice the plasmalemmal thickness. Two types of such synapses were found: (i) uniform (plain) synapses (PS) - close contact extending for > 200 nm, and (ii) multicontact (`kiss and run) synapses (MS) - with multiple, focal, close-contact points alternating with regions of wider intermembrane distance. For instance, a typical PS between a rat bladder ICC-like cell and an eosinophil was 2.48 mu m long and 11 +/- 4nm wide. By contrast, a MS synapse in rat myometrium (between an ICC-like cell and an eosinophil) was 8.64 mu m long and had 13 contact points. The synaptic cleft measured 15 +/- 8nm at contact points and similar to 100nm or more in wider areas. These synapses are different from gap junctions usually seen between ICC and between ICC and smooth muscle cells. We previously proposed that ICC-like cells might represent stromal progenitor cells, participate in juxtacrine/paracrine signaling and play a role in immune surveillance. The nanoscopic distances between the two contiguous membranes suggest a juxtacrine cell-to-cell signaling (chemical synapse), via juxtacrinins, a specific case of phenomenins. However, the (micro)vesicles found in the synaptic cleft may correspond to an exosome-based mechanism.