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.
Bibliographical noteFunding 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.
Copyright 2017 Elsevier B.V., All rights reserved.
- Allogeneic BMT
- Idiopathic pneumonia syndrome