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.
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-gamma and tumor necrosis factor alpha and the chemokines monocyte chemotactic protein 1, macrophage inflammatory protein 1alpha (MIP-1alpha), MIP-1beta, 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.
Panoskaltsis-Mortari
A
A
Department of Pediatrics, University of Minnesota Cancer Center, Minneapolis 55455, USA. panos001@tc.umn.edu
Hermanson
J R
JR
Haddad
I Y
IY
Wangensteen
O D
OD
Blazar
B R
BR
D000818:Animals; D016026:Bone Marrow Transplantation / Q000009:adverse effects* / Q000401:mortality / Q000473:pathology; D018925:Chemokines / Q000096:biosynthesis; D002634:Chemotaxis, Leukocyte; D003106:Colon / Q000473:pathology; D006086:Graft vs Host Disease / Q000209:etiology* / Q000401:mortality / Q000473:pathology; D007111:Immunity, Cellular / Q000502:physiology; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000502:physiology*; D008099:Liver / Q000473:pathology; D008168:Lung / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D011014:Pneumonia / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D014184:Transplantation, Homologous / Q000009:adverse effects / Q000401:mortality / Q000473:pathology
D018925:Chemokines; D018799:Intercellular Adhesion Molecule-1