TY - JOUR
T1 - Simultaneous absence of surfactant proteins A and D increases lung inflammation and injury after allogeneic HSCT in mice
AU - Gram, Kendra
AU - Yang, Shuxia
AU - Steiner, Marie
AU - Somani, Arif
AU - Hawgood, Samuel
AU - Blazar, Bruce R.
AU - Panoskaltsis-Mortari, Angela
AU - Haddad, Imad Y.
PY - 2009/2
Y1 - 2009/2
N2 - 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-α and IFN-γ, were higher in SP-D-deficient mice before and after HSCT. In SP-A/D -/- mice, day 7 post-HSCT BALF levels of TNF-α and IFN-γ, 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.
AB - 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-α and IFN-γ, were higher in SP-D-deficient mice before and after HSCT. In SP-A/D -/- mice, day 7 post-HSCT BALF levels of TNF-α and IFN-γ, 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.
KW - Hematopoietic stem cell transplantation
KW - Idiopathic pneumonia syndrome
KW - Nitric oxide
KW - T cells
KW - Transplantation
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U2 - 10.1152/ajplung.90253.2008
DO - 10.1152/ajplung.90253.2008
M3 - Article
C2 - 18996902
AN - SCOPUS:59449098202
SN - 1040-0605
VL - 296
SP - L167-L175
JO - American Journal of Physiology - Lung Cellular and Molecular Physiology
JF - American Journal of Physiology - Lung Cellular and Molecular Physiology
IS - 2
ER -