Structure and organization of interstitial cells of Cajal in the gastrointestinal tract

Abstract

The morphological features of interstitial cells of Cajal (ICC) in the gastrointestinal (GI) tract are described based on observations of laboratory animals including mice, rats and guinea-pigs, using immunohistochemical staining for Kit and electron microscopy. ICC show a specific distribution, arrangement and cell shape depending on their location within various regions and tissue layers of the GI tract. Hence they are classified into several subtypes. The stomach shows distinct regional variations in the distribution of subtypes of ICC from the cardia to pylorus, whereas the small intestine and colon both seem to retain nearly the same distribution pattern of subtypes of ICC throughout each organ. All subtypes of ICC share common ultrastructural features, such as the presence of numerous mitochondria, abundant intermediate filaments, and formation of gap junctions with the same type of cells and with smooth muscle cells. In addition, depending on their species and anatomical location, some subtypes of ICC show some features typical of smooth muscle cells including a basal lamina, caveolae, subsurface cisterns and dense bodies. ICC are somewhat heterogeneous morphologically. A question is raised on a special relationship between their ultrastructural features and dependency on Kit/stem cell factor system. As the neuromediator function of ICC, reciprocal distribution of ICC and gap junctions in the muscle coat is demonstrated by the comparison of Kit immunoreactive cells and gap junction protein connexin 43 in both small intestine and colon.

Figure 1. Schematic representation of the types of ICC located in different tissue layers of the GI tract

ICC-SMP and ICC-SM are seen at the interface between the submucosa and circular muscle layer in the colon and gastric pylorus, respectively. ICC-DMP are associated with the deep muscular plexus located between the inner and outer circular muscle sublayers in the small intestine. ICC-CM and ICC-LM are found within the circular and longitudinal muscle layers, respectively. ICC-MP are associated with the myenteric plexus between the circular and longitudinal muscle layers. ICC-SS are found in the subserosal connective tissue space. (Reproduced with permission from Hanani et al. 2005.). As to terminology in this article, ICC located in the myenteric (Auerbach's) plexus are designated as ICC-MP instead of ICC-MY or ICC-AP, to keep consistency with the abbreviation for ICC-DMP (deep muscular plexus) and ICC-SMP (submuscular plexus) and because of uncommon usage of the term Auerbach's plexus in the recent literature. ICC-CM and ICC-LM are separately designated, because some morphological and functional differences between them have not been ruled out.

Figure 2. Immunohistochemical staining for Kit and PGP 9.5 to demonstrate cellular networks of ICC (green fluorescence of Alexa 488) and nerves (red fluorescence of TRITC), respectively

a, the network of ICC-MP over the myenteric plexus of the guinea-pig small intestine in which ganglia are orientated parallel to the circular muscle fibres and are connected with thick nerve bundles orientated almost perpendicularly to the ganglia. Scale bar, 80 μm. b, around the myenteric plexus of the guinea-pig colon, ICC-MP are not clearly observed because of their loose arrangement and dense distribution of ICC-CM orientated in a horizontal direction. A few ICC-LM are also seen perpendicularly. Scale bar, 80 μm. c, sparsely distributed ICC–CM in association with rather thick nerve bundles within the circular muscle layer of the guinea-pig small intestine. Scale bar, 40 μm. d, ICC-CM within the circular muscle layer of the guinea-pig gastric corpus. Scale bar, 40 μm.

Figure 3. ICC-CM

ICC-CM in the rat stomach characterized by electron-dense cytoplasm, caveolae (arrows), a gap junction with a smooth muscle cell (double arrow) and a close contact with nerve terminal (N). × 16 000. (Reproduced with permission from Ishikawa et al. 1997.) Scale bar, 1 μm.