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This Article Full Text Full Text (PDF) All Versions of this Article: 296/2/L167    most recent 90253.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Gram, K. Articles by Haddad, I. Y. Search for Related Content PubMed PubMed Citation Articles by Gram, K. Articles by Haddad, I. Y.

Simultaneous absence of surfactant proteins A and D increases lung inflammation and injury after allogeneic HSCT in mice

Department of Pediatrics, Divisions of ¹Pulmonary and Critical Care Medicine and ²Hematology/Oncology and Blood and Marrow Transplant, University of Minnesota, Minneapolis, Minnesota; and ³Department of Pediatrics, Cardiovascular Research Institute, University of California, San Francisco, California

Submitted 31 March 2008 ; accepted in final form 6 November 2008

The relative contributions of the hydrophilic surfactant proteins (SP)-A and -D to early inflammatory responses associated with lung dysfunction after experimental allogeneic hematopoietic stem cell transplantation (HSCT) were investigated. We hypothesized that the absence of SP-A and SP-D would exaggerate allogeneic T cell-dependent inflammation and exacerbate lung injury. Wild-type, SP-D-deficient (SP-D^–/–), and SP-A and -D double knockout (SP-A/D^–/–) C57BL/6 mice were lethally conditioned with cyclophosphamide and total body irradiation and given allogeneic bone marrow plus donor spleen T cells, simulating clinical HSCT regimens. On day 7, after HSCT, permeability edema progressively increased in SP-D^–/– and SP-A/D^–/– mice. Allogeneic T cell-dependent inflammatory responses were also increased in SP-D^–/– and SP-A/D^–/– mice, but the altered mediators of inflammation were not identical. Compared with wild-type, bronchoalveolar lavage fluid (BALF) levels of nitrite plus nitrate, GM-CSF, and MCP-1, but not TNF- and IFN-, were higher in SP-D-deficient mice before and after HSCT. In SP-A/D^–/– mice, day 7 post-HSCT BALF levels of TNF- and IFN-, in addition to nitrite plus nitrate and MCP-1, were higher compared with mice lacking SP-D alone. After HSCT, both SP-A and SP-D exhibited anti-inflammatory lung-protective functions that were not completely redundant in vivo.

T cells; transplantation; nitric oxide; idiopathic pneumonia syndrome; hematopoietic stem cell transplantation