TY - JOUR
T1 - Cytokine and adhesion molecule expression in SCID mice reconstituted with CD4+ T cells
AU - Kawachi, Shigeyuki
AU - Morise, Zenichi
AU - Jennings, Stephen R.
AU - Conner, Elaine
AU - Cockrell, Adam
AU - Laroux, F. Stephen
AU - Chervenak, Robert P.
AU - Wolcott, Michael
AU - Van Der Heyde, Henri
AU - Gray, Laura
AU - Feng, Lan
AU - Granger, D. Neil
AU - Specian, Robert A.
AU - Grisham, Matthew B.
PY - 2000
Y1 - 2000
N2 - The objectives of this study were to quantify colonic cytokine and endothelial cell adhesion molecule (ECAM) expression in the colons of severe combined immunodeficient (SCID) mice reconstituted with different subsets of CD4+ T lymphocytes. We found that animals injected with CD45RBhigh but not CD45RBlow T cells or phosphate-buffered saline (PBS) developed clinical evidence of colitis at 6-8 weeks following reconstitution, as assessed by loss of body weight, development of loose stools and/or diarrhea, and histopathology. Concurrent with the onset of distal bowel inflammation was enhanced expression of a variety of Th1 and macrophage-derived cytokines including interferon γ, tumor necrosis factor-α, interleukin (IL)-1β, IL-6, IL-12, and IL-18 lymphotoxin-β. In addition, message levels and vascular surface expression of ICAM-1, VCAM-1, and MAdCAM-1 were all significantly enhanced in the colitic SCID mice reconstituted with CD45RBhigh T cells compared with SCID mice reconstituted with PBS or CD45RBlow T cells that did not develop disease. Significant increases in some of these ECAMs were also noted in the cecum and stomach and to a lesser degree in the small bowel. Our data confirm that reconstitution of SCID mice with CD45RBhigh but not CD45RBlow T cells induces chronic colitis, and that the colonic inflammation is associated with enhanced expression of proinflammatory cytokines and different ECAMs in the colon. Furthermore, our studies demonstrate that reconstitution of SCID mice with CD45RBhigh T cells enhances ECAM expression in tissues distant from the site of active inflammation.
AB - The objectives of this study were to quantify colonic cytokine and endothelial cell adhesion molecule (ECAM) expression in the colons of severe combined immunodeficient (SCID) mice reconstituted with different subsets of CD4+ T lymphocytes. We found that animals injected with CD45RBhigh but not CD45RBlow T cells or phosphate-buffered saline (PBS) developed clinical evidence of colitis at 6-8 weeks following reconstitution, as assessed by loss of body weight, development of loose stools and/or diarrhea, and histopathology. Concurrent with the onset of distal bowel inflammation was enhanced expression of a variety of Th1 and macrophage-derived cytokines including interferon γ, tumor necrosis factor-α, interleukin (IL)-1β, IL-6, IL-12, and IL-18 lymphotoxin-β. In addition, message levels and vascular surface expression of ICAM-1, VCAM-1, and MAdCAM-1 were all significantly enhanced in the colitic SCID mice reconstituted with CD45RBhigh T cells compared with SCID mice reconstituted with PBS or CD45RBlow T cells that did not develop disease. Significant increases in some of these ECAMs were also noted in the cecum and stomach and to a lesser degree in the small bowel. Our data confirm that reconstitution of SCID mice with CD45RBhigh but not CD45RBlow T cells induces chronic colitis, and that the colonic inflammation is associated with enhanced expression of proinflammatory cytokines and different ECAMs in the colon. Furthermore, our studies demonstrate that reconstitution of SCID mice with CD45RBhigh T cells enhances ECAM expression in tissues distant from the site of active inflammation.
KW - Colitis
KW - ICAM-1
KW - Inflammatory bowel disease
KW - Madcam-1
KW - Neutrophils
KW - VCAM-1
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UR - http://www.scopus.com/inward/citedby.url?scp=0034242809&partnerID=8YFLogxK
U2 - 10.1097/00054725-200008000-00003
DO - 10.1097/00054725-200008000-00003
M3 - Article
C2 - 10961589
AN - SCOPUS:0034242809
SN - 1078-0998
VL - 6
SP - 171
EP - 180
JO - Inflammatory Bowel Diseases
JF - Inflammatory Bowel Diseases
IS - 3
ER -