Interstitial cell of Cajal loss correlates with the degree of inflammation in the human appendix and reverses after inflammation.
BACKGROUND
Normal gut motility relies on the complex interaction between the interstitial cell of Cajal (ICC) and the enteric nerve networks. Inflammation of the gastrointestinal tract adversely affects both ICC and enteric nerves. We aimed to determine the distribution of ICC and nerve networks in patients with appendicitis.


METHODS
Specimens from controls and patients with appendicitis were examined with immunohistochemistry (c-Kit for ICC, beta III tubulin [Tuj-1] and neuronal nitric oxide synthase [histochemical diaphorase] for nitrergic neurons) and electron microscopy (EM). Data were quantified using image analysis.


RESULTS
We found a profound decrease in c-Kit immunoreactivity (c-Kit IR) in the advanced inflammatory stages of appendicitis, which correlated with the severity of inflammation. Electron microscopy confirmed ultrastructural injury in both ICC and nerve fiber networks during acute inflammation. After the inflammation resolved, interval appendices displayed a recovery in ICC c-Kit IR to control levels and normal ultrastructure. The neuronal network also displayed ultrastructural recovery; however, neuronal nitric oxide synthase activity did not recover.


CONCLUSIONS
Severe inflammation results in significant ultrastructural damage of nerves and ICC networks in appendicitis. The loss of c-Kit IR is likely due to impaired ICC cytophysiology because ICC was still present under EM. After resolution of acute inflammation, ICC recovers their normal ultrastructure and c-Kit IR.
Department of General Surgery, Children's Hospital of Eastern Ontario, 401 Smyth Road, Ottawa, Ontario, Canada. mbettolli@cheo.on.ca
Marcos
M
Bettolli
Claudio
C
De Carli
Daniel
D
Cornejo-Palma
Kheira
K
Jolin-Dahel
Xuan-Yu
XY
Wang
Jan
J
Huizinga
Anthony
A
Krantis
Steven
S
Rubin
William A
WA
Staines
D000293:Adolescent; D001064:Appendicitis / Q000276:immunology* / Q000473:pathology*; D001065:Appendix / Q000294:innervation / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D056885:Interstitial Cells of Cajal; D008297:Male; D012720:Severity of Illness Index