Simultaneous absence of surfactant proteins A and D increases lung inflammation and injury after allogeneic HSCT in mice.
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY(2009)
摘要
Gram K, Yang S, Steiner M, Somani A, Hawgood S, Blazar BR, Panoskaltsis-Mortari A, Haddad IY. Simultaneous absence of surfactant proteins A and D increases lung inflammation and injury after allogeneic HSCT in mice. Am J Physiol Lung Cell Mol Physiol 296: L167-L175, 2009. First published November 7, 2008; doi:10.1152/ajplung.90253.2008.-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-alpha and IFN-gamma, were higher in SP-D-deficient mice before and after HSCT. In SP-A/D-/- mice, day 7 post-HSCT BALF levels of TNF-alpha and IFN-gamma, 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.
更多查看译文
关键词
T cells,transplantation,nitric oxide,idiopathic pneumonia syndrome,hematopoietic stem cell transplantation
AI 理解论文
溯源树
样例
生成溯源树,研究论文发展脉络