TY - JOUR
T1 - Intercellular adhesion molecule-I (ICAM-I, CD54) deficiency segregates the unique pathophysiological requirements for generating idiopathic pneumonia syndrome (IPS) versus graft-versus-host disease following allogeneic murine bone marrow transplantation
AU - Panoskaltsis-Mortari, Angela
AU - Hermanson, John R.
AU - Haddad, Imad Y.
AU - Wangensteen, Douglas
AU - Blazar, Bruce R
N1 - Funding Information:
This study was supported by the Children’s Cancer Research Fund, the Viking Children’s Fund, and National Institutes of Health grants R01 HL55952, R01 AI 34495, and P01 AI 35225.
PY - 2001
Y1 - 2001
N2 - Following allogeneic bone marrow transplantation (alloBMT), idiopathic pneumonia syndrome (IPS) and graft-versus-host disease (GVHD) caused by donor cell alloreactivity remain major obstacles to a successful outcome. Intercellular adhesion molecule-1 (ICAM-1) is an adhesion molecule that is involved in regulating lymphohematopoietic cell migration and facilitating T-cell responses. To determine whether ICAM-1 expression in the host would affect IPS or GVHD tissue injury responses, ICAM-1-/- mice were compared with ICAM-1+/+ controls. ICAM-1-/- recipients did not exhibit the manifestations of IPS injury such as an increase in lung weights nor decreased lung function. The influx of T cells, macrophages, and neutrophils was dramatically dampened as was the production of the inflammatory cytokines interferon-γ and tumor necrosis factor α and the chemokines monocyte chemotactic protein 1, macrophage inflammatory protein 1α (MIP-1α), MIP-1β, and lymphotactin, normally upregulated in the lung during IPS. In contrast, systemic levels of these mediators were unaffected and GVHD-induced lesions in the liver and colon did not differ in severity regardless of ICAM-1 expression. GVHD-mediated mortality was accelerated in ICAM-1-/- recipients at doses of allogeneic spleen cells that are otherwise not uniformally lethal. These data implicate ICAM-1 as playing a critical role in the generation of IPS; therefore, ICAM-1 may be a discerning element, segregating IPS from GVHD injury post-alloBMT.
AB - Following allogeneic bone marrow transplantation (alloBMT), idiopathic pneumonia syndrome (IPS) and graft-versus-host disease (GVHD) caused by donor cell alloreactivity remain major obstacles to a successful outcome. Intercellular adhesion molecule-1 (ICAM-1) is an adhesion molecule that is involved in regulating lymphohematopoietic cell migration and facilitating T-cell responses. To determine whether ICAM-1 expression in the host would affect IPS or GVHD tissue injury responses, ICAM-1-/- mice were compared with ICAM-1+/+ controls. ICAM-1-/- recipients did not exhibit the manifestations of IPS injury such as an increase in lung weights nor decreased lung function. The influx of T cells, macrophages, and neutrophils was dramatically dampened as was the production of the inflammatory cytokines interferon-γ and tumor necrosis factor α and the chemokines monocyte chemotactic protein 1, macrophage inflammatory protein 1α (MIP-1α), MIP-1β, and lymphotactin, normally upregulated in the lung during IPS. In contrast, systemic levels of these mediators were unaffected and GVHD-induced lesions in the liver and colon did not differ in severity regardless of ICAM-1 expression. GVHD-mediated mortality was accelerated in ICAM-1-/- recipients at doses of allogeneic spleen cells that are otherwise not uniformally lethal. These data implicate ICAM-1 as playing a critical role in the generation of IPS; therefore, ICAM-1 may be a discerning element, segregating IPS from GVHD injury post-alloBMT.
KW - Allogeneic BMT
KW - ICAM-I
KW - Idiopathic pneumonia syndrome
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U2 - 10.1053/bbmt.2001.v7.pm11529486
DO - 10.1053/bbmt.2001.v7.pm11529486
M3 - Article
C2 - 11529486
AN - SCOPUS:0034858367
SN - 1083-8791
VL - 7
SP - 368
EP - 377
JO - Biology of Blood and Marrow Transplantation
JF - Biology of Blood and Marrow Transplantation
IS - 7
ER -