KGF pretreatment decreases B7 and granzyme B expression and hastens repair in lungs of mice after allogeneic BMT

Angela Panoskaltsis-Mortari, David H. Ingbar, Patricia Jung, Imad Y. Haddad, Peter B. Bitterman, O. Douglas Wangensteen, Catherine L. Farrell, David L. Lacey, Bruce R. Blazar

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42 Scopus citations

Abstract

We investigated keratinocyte growth factor (KGF) as a pretreatment therapy for idiopathic pneumonia syndrome (IPS) generated as a result of lung damage and allogeneic T cell-dependent inflammatory events occurring in the early peri-bone marrow (BM) transplant (BMT) period. B10.BR (H2(k)) recipient mice were transplanted with C57BL/6 (H2b) BM with spleen cells after lethal irradiation with and without cyclophosphamide conditioning with and without subcutaneous KGF pretreatment. KGF-pretreated mice had fewer injured alveolar type II (ATII) cells at the time of BMT and exhibited ATII cell hyperplasia at day 3 post-BMT. The composition of infiltrating cells on day 7 post-BMT was not altered by KGF pretreatment, but the frequencies of cells expressing the T-cell costimulatory molecules B7.1 and B7.2 and mRNA for the cytolysin granzyme B (usually increased in IPS) were decreased by KGF. Sera from KGF- treated mice had increases in the Th2 cytokines interleukin (IL)-4, IL-6, and IL-13 4 days after cessation of KGF administration (i.e., at the time of BMT). These data suggest that KGF hinders IPS by two modes: 1) stimulation of alveolar epithelialization and 2) attenuation of immune-mediated injury as a consequence of failure to upregulate cytolytic molecules and B7 ligand expression and the induction of anti-inflammatory Th2 cytokines in situ.

Original languageEnglish (US)
Pages (from-to)L988-L999
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume278
Issue number5 22-5
DOIs
StatePublished - May 2000

Keywords

  • Bone marrow transplant
  • Costimulatory molecules
  • Cytokines
  • Keratinocyte growth factor
  • Macrophages
  • Type II pneumocytes

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