Background & aims: Submuscular interstitial cells of Cajal (ICC) are putative pacemaker cells of the colonic external muscle. Although motility disturbances and smooth muscle dysfunction are prevalent in patients with ulcerative colitis (UC), ICC have never been studied in this disease. The aim of this study was to examine the ultrastructure of submuscular ICC in UC.
Methods: Transmission electron microscopy of the colonic submuscular region was performed using specimens from 4 adult patients who had undergone resection for severe UC. The specimens were compared with similarly processed control samples.
Results: ICC often showed multiple secondary lysosomes, large confluent lipid bodies, and disrupted aggregates of vacuolated glycogen clusters. Intermediate filaments showed margination and clumping. Intramuscular and submucosal nerve terminals were often swollen. Macrophages were frequent, often close to nerves and ICC. Muscle cells of the innermost circular layer, fibroblast-like cells, and glial cells appeared undisturbed. Other inflammatory cells were inconspicuous.
Conclusions: Alterations of ICC ultrastructure are present in the submuscular pacemaker region of the colon in patients with severe UC. The changes in ICC may result from primary damage or changes secondary to defective muscular function, or they may reflect neuroimmune-mediated metabolic responses. It is suggested that ICC are actively involved in the pathogenesis of motility disturbances in UC.