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

Angela Panoskaltsis-Mortari, John R. Hermanson, Imad Y. Haddad, Douglas Wangensteen, Bruce R Blazar

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)368-377
Number of pages10
JournalBiology of Blood and Marrow Transplantation
Volume7
Issue number7
DOIs
StatePublished - Jan 1 2001

Keywords

  • Allogeneic BMT
  • ICAM-I
  • Idiopathic pneumonia syndrome

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