Vol.:(0123456789) 1 3
Histochem Cell Biol
DOI 10.1007/s00418-017-1563-7
ORIGINAL PAPER
Epithelial cell types and their proposed roles in maintaining
the mucosal barrier in human chagasic–megacolonic mucosa
Christian Koch
1
· Alexandre B. M. da Silveira
2
· Enio C. de Oliveira
3
· Karl Quint
4
·
Winfried Neuhuber
5
· Axel Brehmer
5
· Samir Jabari
5
Accepted: 21 March 2017
© Springer-Verlag Berlin Heidelberg 2017
cells. Gelsolin-positive goblet cells were predominantly
recognized within the controls. Finally, the mean value of
mitosis increased from 1.5% within the controls up to 2.6%
in the anal parts of the chagasic sepcimens. Taken together,
increased cell proliferation, preponderance of goblet cells,
diferential MUC 2, and TFF 3 expression might all be fac-
tors maintaining an intact mucosal barrier within chagasic
megacolon.
Keywords TFF3 · MUC2 · Goblet cells · VIP · Gelsolin ·
Enterocytes · Chagas’ disease · Megacolon
Introduction
About 8 million people in 20 countries of Latin America
are afected from the endemic parasitic condition called
Chagas’ disease (Chagas 1909). 30–40% of patients chroni-
cally infected develop cardiomyopathy and/or digestive
megasyndromes such as megaesophagus or megacolon
(Rassi et al. 2010; Koberle 1968).
We have previously shown that chagasic megacolon is
characterized by a selective, mainly cholinergic neuron loss
in both the myenteric and the submucosal plexus. Very few
nitrergic neurons survive in the myenteric plexus, whereas
numerous neurons, immunoreactive for vasoactive intes-
tinal peptide (VIP), remain in the two submucosal plexus
(Jabari et al. 2011, 2014a). In contrast to the megacolonic
segment in Hirschsprung’s disease which is dilated oral to
the aganglionic segment, the chagasic megacolonic zone is
identical with the location of the (acquired) hypogangliono-
sis (Jabari et al. 2014b).
Remarkably, patients sufering from chagasic megaco-
lon must have an intact mucosal barrier function as they
survive the chronic phase of the disease for decades. Key
Abstract Patients sufering from chagasic megacolon
must have an intact mucosal barrier as they survive this
chronic disease for decades. A key structure of the mucosal
barrier are epithelial cells. Vasoactive-intestinal-peptide
(VIP)-positive nerve fbres are involved in infuencing, e.g.,
epithelial cell proliferation, mucus secretion (e.g., mucin
2 and trefoil factor 3 of goblet cells) and infammation or
autoimmunity, all putative and/or known factors altered in
chagasic megacolon. We analyzed qualitatively and quan-
titatively goblet cells, their specifc markers, such as mucin
2 (MUC2) and trefoil factor 3 (TFF3) and enterocytes, the
relation of VIP-immunoreactive nerve fbres to the epithe-
lia, the distribution of gelsolin, a protein involved in chronic
infammation processes in the epithelia, and the prolifera-
tion rate of epithelial cells by combined 4′,6-diamidino-
2-phenylindole (DAPI) and phosphohistone-H3 (PHH3)
staining. Goblet cells were the dominating epithelial cell
type. They accounted for 38.4% of all epithelial cells in
controls and changed to 58.9% in the megacolonic parts. In
contrast to the overall expression in goblet cells of control
epithelia, TFF3 was confned to goblet cells at the base of
the crypts whereas MUC2 was found only in luminal goblet
* Samir Jabari
samir.jabari@fau.de
1
Waldkrankenhaus St. Marien gGmbH, Rathsberger Straße
57, 91054 Erlangen, Germany
2
Human Anatomy Sector, ICBIM, Universidade Federal de
Uberlândia, Minas Gerais 38.400-902, Brazil
3
Department of Surgery, Medical School, Universidade
Federal de Goiás, Goiás 74.605-020, Brazil
4
Quellenstraße 2, 90556 Cadolzburg, Germany
5
Institute of Anatomy I, University of Erlangen-Nürnberg,
Krankenhausstr. 9, 91054 Erlangen, Germany