Interstitial cells of Cajal, macrophages and mast cells in the gut musculature: morphology, distribution, spatial and possible functional interactions

Abstract

Interstitial cells of Cajal (ICC) are recognized as pacemaker cells for gastrointestinal movement and are suggested to be mediators of neuromuscular transmission. Intestinal motility disturbances are often associated with a reduced number of ICC and/or ultrastructural damage, sometimes associated with immune cells. Macrophages and mast cells in the intestinal muscularis externa of rodents can be found in close spatial contact with ICC. Macrophages are a constant and regularly distributed cell population in the serosa and at the level of Auerbach’s plexus (AP). In human colon, ICC are in close contact with macrophages at the level of AP, suggesting functional interaction. It has therefore been proposed that ICC and macrophages interact. Macrophages and mast cells are considered to play important roles in the innate immune defence by producing pro-inflammatory mediators during classical activation, which may in itself result in damage to the tissue. They also take part in alternative activation which is associated with anti-inflammatory mediators, tissue remodelling and homeostasis, cancer, helminth infections and immunophenotype switch. ICC become damaged under various circumstances – surgical resection, possibly post-operative ileus in rodents – where innate activation takes place, and in helminth infections – where alternative activation takes place. During alternative activation the muscularis macrophage can switch phenotype resulting in up-regulation of F4/80 and the mannose receptor. In more chronic conditions such as Crohn’s disease and achalasia, ICC and mast cells develop close spatial contacts and piecemeal degranulation is possibly triggered.

Irritable bowel syndrome, the microbiota and the gut-brain axis

“…73 During inflammation MM participate in the regulation of gut motility by secretion of inflammatory cytokines and recruitment of inflammatory cells. 74 MM impact on GI motility during normal physiological conditions through the production of BMP2 protein (bone morphogenetic protein 2), which activates BMP receptors expressed by enteric neurons. In turn neurons secrete CSF1 (colony stimulating factor 1) essential for MM development.…”

Interstitial Cells of Cajal : Pathology , Injury and Repair = خلايا كاجال الخلالية : علم الأمراض و الإصابات و الإصلاح

“…Taken together, these factors help to repair injured ICC. 42,43 Thus the close contact between activated macrophages and ICC would eventually affect ICC both when pro-inflammatory or antiinflammatory cytokines and growth factors are produced by macrophages in response to infection, inflammation, and surgical manipulation. Another source for replenishing ICC in disease states is the local reserve of ICC progenitor or stem cells.…”

663 Association of Low Numbers of CD206-Positive Cells With Loss of ICC in the Gastric Body of Patients With Diabetic Gastroparesis

“…All macrophages in the mouse stomach are immuno-labeled with F4/80, a monoclonal antibody against a membrane glycoprotein, this includes resident, classically activated and alternatively activated macrophages. 16,17 Classically activated macrophages, also known as M1 macrophages, express inducible nitric oxide synthase (iNOS, NOS2) among other markers and nitric oxide (NO) is an important cytotoxic product of these cells. 18,19 Alternatively activated or M2 macrophages express the mannose receptors (CD206) and heme oxygenase-1 (HO1) and mediate cell repair and have anti-inflammatory roles.…”

“…27 Identification of the involvement of macrophages may identify new therapeutic targets but there has been limited characterization of macrophages in the muscularis propria of human gastrointestinal tissue. 17,[28][29][30] In this study, we assessed the reliability of HAM56, CD68 and EMR1 as selective markers of macrophages in human gastric muscularis propria. We also quantified CD45 positive cells as a measure of general immune cell infiltrate in tissues from patients with diabetic and idiopathic gastroparesis, quantified CD206 positive cells as a measure of anti-inflammatory macrophages, quantified iNOS positive cells as a measure of an increased inflammatory environment in the tissues, and studied the relationship between CD45, CD206, and iNOS positive cell numbers and ICC numbers.…”