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

Abstract

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 ∼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 μm long and 11±4nm wide. By contrast, a MS synapse in rat myometrium (between an ICC-like cell and an eosinophil) was 8.64 μm long and had 13 contact points. The synaptic cleft measured 15±8nm at contact points and ∼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.