Mast cells and macrophages in duodenal mucosa of mice overexpressing erythropoietin.
There is increasing evidence suggesting a wider biological role of erythropoietin (Epo) and Epo receptor (EpoR) not related to erythropoiesis, such as the detection of EpoR in other cells, i.e. polymorphonuclear leukocytes, megakaryocytes, endothelial, myocardial and neural cells. In this study, by using a mouse model (designated tg6) that constitutively overexpresses human Epo in an oxygen-independent manner, we have investigated mast cell and macrophage number and distribution in duodenal mucosa using immunohistochemical, morphometric and image analysis methods. The results showed that tryptase-positive mast cells and BM8-positive macrophages were more numerous in duodenal mucosa specimens of tg6 mice compared with wild-type mice. Moreover, whereas in wild-type specimens both mast cells and macrophages were generally scattered throughout the villus, in tg6 specimens they were aligned along the axis of the villus. Morphometric analysis confirms this observation, and the quantitative analysis of the spatial distribution of the cells in duodenal villi indicated that in both wild-type and tg6 groups the macrophage and mast cell distribution was characterized by significant deviations from randomness. In addition, an increased number of c-kit-positive cells have been identified in the villus axis of tg6 mice, indicating an expanded compartment of mast cell precursors in the intestinal mucosa of these animals. Finally, we have also demonstrated that in tg6 specimens the number of duodenal epithelial cells positive for Epo were significantly higher as compared to wild type. Overall, these data confirm that Epo, acting as a general stimulator of the hemopoietic compartment, is able to induce an expansion of two effectors of the immune response, mast cells and macrophages, in a specific peripheral site, the duodenal mucosa, in the tg6 mouse experimental model.
Ribatti
Domenico
D
Department of Human Anatomy and Histology, University of Bari Medical School, Bari, Italy. ribatti@anatomia.uniba.it
Crivellato
Enrico
E
Nico
Beatrice
B
Guidolin
Diego
D
Gassmann
Max
M
Djonov
Valentin
V
D000818:Animals; D002452:Cell Count; D004386:Duodenum / Q000166:cytology* / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D004921:Erythropoietin / Q000378:metabolism*; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D007413:Intestinal Mucosa / Q000166:cytology* / Q000378:metabolism; D008264:Macrophages / Q000166:cytology*; D008297:Male; D008407:Mast Cells / Q000166:cytology*; D051379:Mice; D008822:Mice, Transgenic; D053802:Tryptases / Q000378:metabolism
D004921:Erythropoietin; D053802:Tryptases
Eur J Immunol. 2007 Jun;37(6):1584-93
17458859
Immunity. 2002 Sep;17(3):277-88
12354381
Blood. 2002 Dec 15;100(13):4272-90
12393615
Blood. 1997 Aug 15;90(4):1345-64
9269751
J Cereb Blood Flow Metab. 2001 Jul;21(7):857-64
11435798
Mol Immunol. 2009 Feb;46(4):713-21
19027957
Am J Physiol Regul Integr Comp Physiol. 2006 Oct;291(4):R947-56
16690772
Blood. 2001 Jan 15;97(2):536-42
11154234
Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):3974-8
8171022
Cell Tissue Res. 1986;243(2):421-8
3948241
Blood. 1996 Apr 1;87(7):2702-13
8639886
Blood. 1978 Aug;52(2):447-52
352443
Am J Physiol Regul Integr Comp Physiol. 2006 Mar;290(3):R678-84
16254128
Adv Exp Med Biol. 2002;512:1-10
12405181
Cardiovasc Drugs Ther. 2007 Feb;21(1):17-27
17297593
Nephron. 2001 Jul;88(3):205-10
11423750
Genes Dev. 1996 Jan 15;10(2):154-64
8566749
Int J Mol Med. 2006 Jun;17(6):981-7
16685405
Early Hum Dev. 1998 Oct;52(3):235-49
9808074
Arch Dermatol Res. 2006 Mar;297(9):389-94
16421725
J Neuropathol Exp Neurol. 2003 Mar;62(3):228-36
12638727
Blood. 1999 Apr 15;93(8):2627-36
10194442
Blood. 2003 Sep 15;102(6):2278-84
12750170
Exp Hematol. 1989 Jan;17(1):10-6
2535696
Cell. 1995 Oct 6;83(1):59-67
7553874
Neurosurgery. 1991 Jan;28(1):24-6
1994278
Proc Natl Acad Sci U S A. 1995 Apr 25;92(9):3717-20
7731971
Histopathology. 1996 Jan;28(1):1-13
8838115
Proc Natl Acad Sci U S A. 2000 Oct 10;97(21):11609-13
11027359
Proc Natl Acad Sci U S A. 1998 Apr 14;95(8):4635-40
9539790
J Struct Biol. 2000 Dec;132(3):201-10
11243889
Blood. 2007 Jul 15;110(2):762-9
17395782
Immunol Lett. 2008 Aug 15;119(1-2):22-31
18601952
Growth Factors. 1999;17(1):25-35
10495960
Acta Neurochir (Wien). 1987;85(1-2):56-62
3300179
Mol Cell Biol. 1991 May;11(5):2901-4
1708097
Blood. 2004 Sep 15;104(6):1688-95
15178584
Glia. 2000 May;30(3):271-8
10756076