Background: CIIP is a gastrointestinal motility disorder mimicking bowel obstruction in the absence of any lesions occluding the gut lumen. A number of degenerative and inflammatory factors can contribute to enteric neuromuscular abnormalities underlying dysmotility in CIIP. The detection of an inflammatory neuro-myopathies at histopathology may have a special impact in the management of CIIP patients because of obvious therapeutic implications. Aim: From a single center-studied patient cohort, we investigated: 1) CIIP patients with an associated inflammatory neuro-myopathy; 2) clinical, morphological and molecular correlates of those CIIP patients with identified neuro-muscular inflammatory changes. Methods: Thirty consecutive patients (22 F, 8 M; age range: 16-63 yrs) with clinically established and manometrically characterized CIIP underwent laparoscopic surgery to collect ileal full-thickness biopsies for histopathology. Tissue samples from n=4 pts with uncomplicated gut neoplastic disease served as controls. Biopsies were processed for classic H&E and immunohistochemical analysis using a variety of markers for neurons and glia (NSE, NF, Synaptophysin, S100), neurochemical messengers (NOS, VIP, NPY, CGRP, SP/TK), neuronal apoptosis (Bcl-2), interstitial cells of Cajal (ICC, c-Kit) and smooth muscle (actin, myosin, dystophin, caldesmon and COX). Also, antibodies detecting lymphocytes (CD45), macrophages (CD68) and mast cells (c-kit and tryptase) were used. Expression of mRNA coding for COX and NOS isoforms was assessed by reverse transcription (RT) polimerase chain reaction (PCR) on ileal specimens snap-frozen in liquid nitrogen. Results: Among all investigated CIIP patients, ileal biopsies from 11 pts (36%) (10 F, 1 M; age range: 28-63 yrs) had an apparently normal structure as compared to controls. Specifically, enteric plexuses/nerve fibers were normal as demonstrated by the previously mentioned markers. Similarly, c-Kit positive ICC networks and unchanged muscular layers were reported. Both CD45 and CD68 did not reveal immunocytes throughout the neuromuscular layer, while c-Kit and tryptase labeling identified dense mast cell infiltrate not only in the mucosa and submucosa, but also spreading to the neuromuscular component. In association with this finding, a reduced nNOS immunolabeling was detected in about 4/11 (36%) of the positive cases. RT-PCR analysis revealed the expression of COX-1, COX-2, eNOS, iNOS and nNOS… The densitometric analysis… Conclusions: A relevant subset of CIIP pts from a single center cohort showed a neuromuscular mast cell infiltrate as unique histopathologic hallmark. The abnormalities to COX and NOS expression suggest a mast cell dependent mechanisms leading to neuromuscular dysfunction contributing to CIIP in such a context. The present data pave the way targeting mast cell if these infiltrate can be detected in the neuromuscular layer of CIIP pts.

Mast cell neuromuscolar involvement in patients with severe gastrointestinal dysmotility (SGID)

COLUCCI, ROCCHINA LUCIA;BERNARDINI, NUNZIA;BLANDIZZI, CORRADO;DEL TACCA, MARIO;
2007

Abstract

Background: CIIP is a gastrointestinal motility disorder mimicking bowel obstruction in the absence of any lesions occluding the gut lumen. A number of degenerative and inflammatory factors can contribute to enteric neuromuscular abnormalities underlying dysmotility in CIIP. The detection of an inflammatory neuro-myopathies at histopathology may have a special impact in the management of CIIP patients because of obvious therapeutic implications. Aim: From a single center-studied patient cohort, we investigated: 1) CIIP patients with an associated inflammatory neuro-myopathy; 2) clinical, morphological and molecular correlates of those CIIP patients with identified neuro-muscular inflammatory changes. Methods: Thirty consecutive patients (22 F, 8 M; age range: 16-63 yrs) with clinically established and manometrically characterized CIIP underwent laparoscopic surgery to collect ileal full-thickness biopsies for histopathology. Tissue samples from n=4 pts with uncomplicated gut neoplastic disease served as controls. Biopsies were processed for classic H&E and immunohistochemical analysis using a variety of markers for neurons and glia (NSE, NF, Synaptophysin, S100), neurochemical messengers (NOS, VIP, NPY, CGRP, SP/TK), neuronal apoptosis (Bcl-2), interstitial cells of Cajal (ICC, c-Kit) and smooth muscle (actin, myosin, dystophin, caldesmon and COX). Also, antibodies detecting lymphocytes (CD45), macrophages (CD68) and mast cells (c-kit and tryptase) were used. Expression of mRNA coding for COX and NOS isoforms was assessed by reverse transcription (RT) polimerase chain reaction (PCR) on ileal specimens snap-frozen in liquid nitrogen. Results: Among all investigated CIIP patients, ileal biopsies from 11 pts (36%) (10 F, 1 M; age range: 28-63 yrs) had an apparently normal structure as compared to controls. Specifically, enteric plexuses/nerve fibers were normal as demonstrated by the previously mentioned markers. Similarly, c-Kit positive ICC networks and unchanged muscular layers were reported. Both CD45 and CD68 did not reveal immunocytes throughout the neuromuscular layer, while c-Kit and tryptase labeling identified dense mast cell infiltrate not only in the mucosa and submucosa, but also spreading to the neuromuscular component. In association with this finding, a reduced nNOS immunolabeling was detected in about 4/11 (36%) of the positive cases. RT-PCR analysis revealed the expression of COX-1, COX-2, eNOS, iNOS and nNOS… The densitometric analysis… Conclusions: A relevant subset of CIIP pts from a single center cohort showed a neuromuscular mast cell infiltrate as unique histopathologic hallmark. The abnormalities to COX and NOS expression suggest a mast cell dependent mechanisms leading to neuromuscular dysfunction contributing to CIIP in such a context. The present data pave the way targeting mast cell if these infiltrate can be detected in the neuromuscular layer of CIIP pts.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11568/117165
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