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

• Published in: American journal of physiology. Lung cellular and molecular physiology 2000-05, Vol.278 (5), p.988-L999
• Main Authors: Panoskaltsis-Mortari, Angela, Ingbar, David H, Jung, Patricia, Haddad, Imad Y, Bitterman, Peter B, Wangensteen, O. Douglas, Farrell, Catherine L, Lacey, David L, Blazar, Bruce R
• Format: Article
• Language: English
• Subjects: AIDS/HIV; Animals; Antigens, CD - genetics; B7-1 Antigen - genetics; B7-2 Antigen; Bone Marrow Transplantation - adverse effects; Bone Marrow Transplantation - immunology; Fibroblast Growth Factor 10; Fibroblast Growth Factor 7; Fibroblast Growth Factors; Gene Expression - immunology; Granzymes; Growth Substances - pharmacology; Hypersensitivity - immunology; In Situ Hybridization; Interleukin-13 - blood; Interleukin-13 - genetics; Interleukin-13 - immunology; Interleukin-4 - blood; Interleukin-4 - genetics; Interleukin-4 - immunology; Interleukin-6 - blood; Interleukin-6 - immunology; Macrophages, Alveolar - immunology; Membrane Glycoproteins - genetics; Mice; Mice, Inbred C57BL; Microscopy, Electron; Monocytes - immunology; Pneumonia - etiology; Pneumonia - immunology; Pulmonary Alveoli - enzymology; Pulmonary Alveoli - immunology; Pulmonary Alveoli - ultrastructure; RNA, Messenger - analysis; Serine Endopeptidases - genetics; Th2 Cells - immunology; Transplantation Conditioning
• ISSN: 1040-0605; 1522-1504
• DOI: 10.1152/ajplung.2000.278.5.l988

1  Department of Pediatrics, Division of Hematology-Oncology and Bone Marrow Transplantation, and Departments of 2  Pulmonary Critical Care Medicine and 3  Physiology, University of Minnesota, Minneapolis, Minnesota 55455; and 4  Amgen, Thousand Oaks, California 91320 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 (H2 b ) 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. bone marrow transplant; keratinocyte growth factor; type II pneumocytes; cytokines; macrophages; costimulatory molecules