Acceleration of idiopathic pneumonia syndrome (IPS) in the absence of donor MIP-1α (CCL3) after allogeneic BMT in mice

Angela Panoskaltsis-Mortari, John R. Hermanson, Elizabeth Taras, O. Douglas Wangensteen, Jonathan S. Serody, Bruce R. Blazar

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30 Scopus citations


Idiopathic pneumonia syndrome (IPS) is a significant cause of morbidity and mortality after bone marrow transplantation (BMT) in humans. We developed a murine IPS model in which lethal pre-BMT conditioning and allogeneic T cells results in the recruitment of host monocytes and then donor T cells into the lung by day 7 after BMT, concomitant with development of severe lung dysfunction. We reported the T cell-dependent production of the T cell-attracting chemokine macrophage inflammatory protein-1α (MIP-1α) in the lungs of such recipient mice. We reasoned that MIP-1α might be a critical mediator of IPS. Lethally conditioned mice received transplants of major histocompatibility complex-disparate marrow and either wild-type (MIP-1α+/+) or knockout (MIP-1α-/-) spleen cells. Recipients of MIP-1α-/- cells exhibited accelerated mortality and a decrease in specific compliance that appeared earlier than in recipients of MIP-1α+/+ cells. Donor CD4+ and CD8+ T cell expansion was increased in the spleens of recipients of MIP-1α-/- cells. Lungs of recipients of MIP-1α-/- cells had earlier recruitment of both T-cell subsets by day 3 after BMT, concomitant with the influx of cells expressing the cytolysins granzymes A and B. Monocyte recruitment was not altered. Levels of inflammatory cytokines were not increased and levels of T cell-attracting chemokines were decreased. The level of the anti-inflammatory cytokine interleukin 13 (IL-13) was lower in the serum and lungs of recipients of MIP-1α-/- cells, indicating a skewing toward a more inflammatory T helper cell type 1 (Th1) cytokine milieu. Donor-derived MIP-1α may play a role in allogeneic-induced IPS by limiting aggressive expansion of CD4+ and CD8+ T cells.

Original languageEnglish (US)
Pages (from-to)3714-3721
Number of pages8
Issue number9
StatePublished - May 1 2003


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