TY - JOUR
T1 - A Role for TNF Receptor Type II in Leukocyte Infiltration into the Lung during Experimental Idiopathic Pneumonia Syndrome
AU - Hildebrandt, Gerhard C.
AU - Olkiewicz, Krystyna M.
AU - Corrion, Leigh
AU - Clouthier, Shawn G.
AU - Pierce, Elizabeth M.
AU - Liu, Chen
AU - Cooke, Kenneth R.
N1 - Funding Information:
This work was supported by grants 5R01 HL072258-03, R01 HL55162-05, and from the Walther Cancer Institute.
PY - 2008/4
Y1 - 2008/4
N2 - Idiopathic pneumonia syndrome (IPS) is a frequently fatal complication following allogeneic stem cell transplantation (allo-SCT). Experimental models have revealed that TNF-α contributes to pulmonary vascular endothelial cell (EC) apoptosis, and modulates the infiltration of donor leukocytes into the lung parenchyma. The inflammatory effects of TNF-α are mediated by signaling through the type I (TNFRI) or type II (TNFRII) TNF receptors. We investigated the relative contribution of TNFRI and TNFRII to leukocyte infiltration into the lung following allo-SCT by using established murine models. Wild-type (wt) B6 mice or B6 animals deficient in either TNFRI or TNFRII were lethally irradiated and received SCT from allogeneic (LP/J) or syngeneic (B6) donors. At week 5 following SCT, the severity of IPS was significantly reduced in TNFRII-/- recipients compared to wt controls, but no effect was observed in TNFRI-/- animals. Bronchoalveolar lavage fluid (BALF) levels of RANTES and pulmonary ICAM-1 expression in TNFRII-/- recipients were also reduced, and correlated with a reduction of CD8+ cells in the lung. Pulmonary inflammation was also decreased in TNFRII-/- mice using an isolated MHC class I disparate model (bm1 → B6), and in bm1 wt mice transplanted with B6 TNF-α-/- donor cells. Collectively, these data demonstrate a role for TNF-α signaling through TNFRII in leukocyte infiltration into the lung following allo-SCT, and suggest that disruption of the TNF-α:TNFRII pathway may be an effective tool to prevent or treat IPS.
AB - Idiopathic pneumonia syndrome (IPS) is a frequently fatal complication following allogeneic stem cell transplantation (allo-SCT). Experimental models have revealed that TNF-α contributes to pulmonary vascular endothelial cell (EC) apoptosis, and modulates the infiltration of donor leukocytes into the lung parenchyma. The inflammatory effects of TNF-α are mediated by signaling through the type I (TNFRI) or type II (TNFRII) TNF receptors. We investigated the relative contribution of TNFRI and TNFRII to leukocyte infiltration into the lung following allo-SCT by using established murine models. Wild-type (wt) B6 mice or B6 animals deficient in either TNFRI or TNFRII were lethally irradiated and received SCT from allogeneic (LP/J) or syngeneic (B6) donors. At week 5 following SCT, the severity of IPS was significantly reduced in TNFRII-/- recipients compared to wt controls, but no effect was observed in TNFRI-/- animals. Bronchoalveolar lavage fluid (BALF) levels of RANTES and pulmonary ICAM-1 expression in TNFRII-/- recipients were also reduced, and correlated with a reduction of CD8+ cells in the lung. Pulmonary inflammation was also decreased in TNFRII-/- mice using an isolated MHC class I disparate model (bm1 → B6), and in bm1 wt mice transplanted with B6 TNF-α-/- donor cells. Collectively, these data demonstrate a role for TNF-α signaling through TNFRII in leukocyte infiltration into the lung following allo-SCT, and suggest that disruption of the TNF-α:TNFRII pathway may be an effective tool to prevent or treat IPS.
KW - Cytokines
KW - Graft-versus-host disease
KW - Stem cell transplantation
KW - TNF-α
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U2 - 10.1016/j.bbmt.2008.01.004
DO - 10.1016/j.bbmt.2008.01.004
M3 - Article
C2 - 18342780
AN - SCOPUS:40649127479
SN - 1083-8791
VL - 14
SP - 385
EP - 396
JO - Biology of Blood and Marrow Transplantation
JF - Biology of Blood and Marrow Transplantation
IS - 4
ER -