In the Forum
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
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.
c-kit is not a specific marker and is expressed by a variety of other cell types
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.
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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.
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Harhun MI, Pucovsky V, Povstyan OV, Gordienko DV, Bolton TB. 2005. Interstitial cells in the vasculature. J Cell Mol Med 9:232-43
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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.
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