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

Kendra Gram, Shuxia Yang, Marie Steiner, Arif Somani, Samuel Hawgood, Bruce R. Blazar, Angela Panoskaltsis-Mortari, Imad Y. Haddad

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)L167-L175
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume296
Issue number2
DOIs
StatePublished - Feb 2009

Keywords

  • Hematopoietic stem cell transplantation
  • Idiopathic pneumonia syndrome
  • Nitric oxide
  • T cells
  • Transplantation

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