Morphological evaluation of the colonic mucosa in chronic slow-transit constipation based on immunohistochemical study

Major pathological processes, primarily inflammatory ones, are associated with disruption of the barrier function of the gastrointestinal mucosa. The structures of the nervous system that interact with cells of innate and adaptive immunity and modulate intestinal function remain insufficiently studied.

This work aimed to examine the human colonic mucosa in chronic slow-transit constipation (CSTC) using five clinical cases and to characterize the relationships between the mucosa, neural, and glial structures.

Immunohistochemical examination was performed on fragments of the descending colon mucosa obtained during surgical treatment of patients with severe CSTC. To identify inflammatory and immune cells, toluidine blue staining was used along with antibodies to CD68 and Iba-1 (ionized calcium-binding adaptor molecule 1) — macrophage markers; tryptase — a mast cell marker; PGP 9.5 (protein gene product 9.5), synaptophysin, and tyrosine hydroxylase — to detect neural structures; S100β protein — a glial marker; and serotonin and chromogranin A — markers of enterochromaffin cells.

In all examined cases of CSTC, hypertrophy of the lamina propria and leukocytic infiltrates were detected in the colonic mucosa, consisting mainly of blast forms of lymphocytic and monocyte–macrophage lineages (Iba-1⁺ and CD68⁺ cells), as well as mast cells. It was established that the innervation of the mucosal tissues involves postganglionic cholinergic fibers originating from neurons of the submucosal plexus microganglia. They are forming en passant terminal synaptic networks composed of varicose axonal bundles and accompanying neurolemmocytes. Close intercellular interactions were observed between parasympathetic nerve endings and glial elements, as well as immune–inflammatory cells. There was no sympathetic innervation of the mucosal tissues.

The presence of leukocytic infiltrates in the colonic mucosa of patients with CSTC, its intense innervation, and the accumulation of enterochromaffin cells in the epithelium indicate neurogenic inflammation. The inflammation affects the permeability of the enteral epithelium and modulates immune responses aimed at maintaining tissue homeostasis and restoring the barrier function of the intestinal wall mucosa in CSTC.