Arterial Interstitial Cells of Cajal – Comment

In
the 1890s, Santiago Ramon y Cajal described distinctive cells in the
small intestine. These cells are special cells with processes
interposed between nerve endings and smooth muscle cells in the
gastrointestinal tract. It has been established that some ICC in the
gastrointestinal tract are pacemaker cells. It has become clear that
ICC are
distributed more widely throughout the body than was previously thought
(Huizinga and Faussone-Pellegrini, 2005). Recently, ICC-like cells were
identified in the urogenital tract (Sergeant et al., 2000; Metzger et
al., 2004; Duquette et al., 2005). A very recent publication reports
the presence of ICC in the pancreas (Popescu et al., 2005). The findings of ICC-like cells outside the gastrointestinal tract supports the opinion of Takayama et al.
(2002) and Takaki (2003) and others who have suggested that some ICC
are not pacemakers but rather are interposed between nerve endings and
smooth muscle cells and have different and yet unknown functions.

Dr. Yuri V. Bobryshev (y.bobryshev@unsw.edu.au) is Senior Research Associate at the Surgical Professorial Unit, St. Vincent’s hospital Syndey.

A
possibility that ICC-like cells may be present in the arteries has been
discussed for a long time (Meyling, 1953; Dahl and Nelson 1964; Dahl et
al. 1965; Lee 1995). In 2003, non-contractile cells with physiological
characteristics similar of intestinal ICC were purified from guinea-pig
mesenteric arteries (Pucovsky et al. 2003, Bolton et al. 2004; Harhun
et al. 2005). Recently, cells with ultrastructural features of
intestinal ICC were identified in human large arteries (Bobryshev
2005). These ICC-like cells were found located at the media-adventitia
border of the arterial wall where ICC-like cells form direct contacts
with both nerve endings and smooth muscle cells (Bobryshev 2005). This
localization of arterial ICC-like cells suggests that the cells might
be involved as intermediaries in neuronal transmission and regulation
of the function of smooth muscle cells. Supporting this possibility is
the finding that, at the arterial media-adventitia border, ICC-like
cells intensely express neurokinin receptor-1 and form direct contacts with substance P-positive nerve endings (Bobryshev 2005).

Arterial ICC-like cells were found to be negative for c-kit (Pucovsky et al. 2003, Harhun et al. 2005; Bobryshev 2005),
which is the most commonly used marker for the identification of ICC in
the gastrointestinal tract (Faussone-Pellegrini and Thuneberg 1999;
Vanderwinden and Rumessen 1999). However, it is well known that not all
ICC in the gastrointestinal tract express c-kit (Faussone-Pellegrini
and Thuneberg 1999; Vanderwinden and Rumessen 1999). Moreover, c-kit is
not a specific marker and is expressed by a variety of other cell types
including mast cells and stem cells in the arterial wall (Hu et al. 2004; Hibbert et al.,
2004; Bobryshev 2005). At present, there is no unique marker for the
unambiguous immunohistochemical identification of AICC. In the absence
of a unique immunochemical marker, electron microscopy remains “the
gold standard” for the identification of ICC (Komuro et al. 1996;
Komuro et al, 1999; Faussone-Pellegrini and Thuneberg 1999;
Vanderwinden and Rumessen 1999, Bobryshev 2005).

ICC-like cells in arteries were designated as “Arterial Interstitial Cells of Cajal
“(AICC) (Bobryshev 2005). This term indicates their similarity to ICC
of the gastrointestinal tract and to other ICC-like cells recently
identified in the urogenital tract and the pancreas (Metzger et al., 2004; Duquette et al., 2005; Popescu et al., 2005). This term is also suggestive of possible unique properties.

The
investigation of AICC is in its infancy. Further investigations might
have important implications for understanding the contribution of AICC
in a variety of vascular diseases.

Now read our Minireview of Arterial Interstitial Cells of Cajal

References

Bobryshev
YV. 2005. Subset of cells immunopositive for neurokinin-1 receptor
identified as arterial interstitial cells of Cajal in human large
arteries. Cell Tissue Res (in press)

Bolton
TB, Gordienko DV, Povstyan OV, Harhun MI, Pucovsky V. 2004. Smooth
muscle cells and interstitial cells of blood vessels. Cell Calcium.
2004 35:643-57

Dahl E, Nelson E. 1964. Electron microscopic observations on human intracranial arteries. Arch Neurol 10:158-64.

Dahl E, Flora G, Nelson E. 1965. Electron microscopic observations on normal human intracranial arteries. Neurology 15:132-40

Duquette
RA, Shmygol A, Vaillant C, Mobasheri A, Pope M, Burdyga T, Wray S.
2005. Vimentin-positive, c-kit-negative interstitial cells in human and
rat uterus: a role in pacemaking? Biol Reprod 72:276-83.

Faussone-Pellegrini MS, Thuneberg L.1999. Guide to the identification of interstitial cells of Cajal. Microsc Res Tech 47:248-66

Harhun
MI, Pucovsky V, Povstyan OV, Gordienko DV, Bolton TB. 2005.
Interstitial cells in the vasculature. J Cell Mol Med 9:232-43

Hibbert
B, Chen YX, O’Brien ER. 2004. c-kit-immunopositive vascular progenitor
cells populate human coronary in-stent restenosis but not primary
atherosclerotic lesions. Am J Physiol Heart Circ Physiol 287:H518-24

Huizinga
JD, Faussone-Pellegrini MS. 2005. About the presence of interstitial
cells of Cajal outside the musculature of the gastrointestinal tract. J
Cell Mol Med.9:468-73

Hu
Y, Zhang Z, Torsney E, Afzal AR, Davison F, Metzler B, Xu Q. 2004.
Abundant progenitor cells in the adventitia contribute to
atherosclerosis of vein grafts in ApoE-deficient mice. J Clin Invest
113:1258-65.

Lee RM. 1995. Morphology of cerebral arteries. Pharmacol Ther 66:149-73

Meyling
HA. 1953. Structure and significance of the peripheral extension of the
autonomic nervous system. J Comp Neurol. 99:495-43

Metzger
R, Schuster T, Till H, Stehr M, Franke FE, Dietz HG.2004. Cajal-like
cells in the human upper urinary tract. J Urol 172:769-72

Popescu
LM, Hinescu ME, Ionescu N, Ciontea SM, Cretoiu D, Ardelean C. 2005.
Interstitial cells of Cajal in pancreas. J Cell Mol Med 9:169-90

Pucovsky
V, Moss RF, Bolton TB. 2003. Non-contractile cells with thin processes
resembling interstitial cells of Cajal found in the wall of guinea-pig
mesenteric arteries. J Physiol 552:119-33.

Sergeant
GP, Hollywood MA, McCloskey KD, Thornbury KD, McHale NG. 2000.
Specialised pacemaking cells in the rabbit urethra. J Physiol 526:359-66

Takaki M. Gut pacemaker cells: the interstitial cells of Cajal (ICC).2003. J Smooth Muscle Res. 39:137-61

Takayama
I, Horiguchi K, Daigo Y, Mine T, Fujino MA, Ohno S. 2002. The
interstitial cells of Cajal and a gastroenteric pacemaker system. Arch
Histol Cytol 65:1-26

Vanderwinden
JM, Rumessen JJ. 1999. Interstitial cells of Cajal in human gut and
gastrointestinal disease. Microsc Res Tech 47:344-60

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