Intercellular adhesion molecule-1 (ICAM-1, CD54) deficiency segregates theunique pathophysiological requirements for generating idiopathic pneumoniasyndrome (IPS) versus graft-versus-host disease following allogeneic murine bone marrow transplantation

Following allogeneic bone marrow transplantation (alloBMT), idiopathic pneu monia syndrome (TPS) and graft-versus-host disease (GVHD) caused by donor c ell alloreactivity remain major obstacles to a successful outcome. Intercel lular adhesion molecule-1 (ICAM-1) is an adhesion molecule that is involved in regulating lymphohematopoietic cell migration and facilitating T-cell r esponses. To determine whether ICAM-1 expression in the host would affect I PS or GVHD tissue injury responses, ICAM-1(-/-) mice were compared with ICA M-1(+/+) controls. ICAM-1(-/-) recipients did not exhibit the manifestation s of IPS injury such as an increase in lung weights nor decreased lung func tion. The influx of T cells, macrophages, and neutrophils was dramatically dampened as was the production of the inflammatory cytokines interferon-gam ma and tumor necrosis factor a and the chemokines monocyte chemotactic prot ein 1, macrophage inflammatory protein 1 alpha (MIP-1 alpha), MIP-1 beta, a nd 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 exp ression. GVHD-mediated mortality was accelerated in ICAM-1(-/-) recipients at doses of allogeneic spleen cells that are otherwise not uniformally leth al. These data implicate ICAM-1 as playing a critical role in the generatio n of IPS; therefore, ICAM-1 may be a discerning element, segregating IPS fr om GVHD injury post-alloBMT.