Surfactant protein A is a required mediator of keratinocyte growth factor after experimental marrow transplantation

Imad Y. Haddad, Carlos Milla, Shuxia Yang, Angela Panoskaltsis-Mortari, Samuel Hawgood, David L. Lacey, Bruce R. Blazar

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


We reported an association between the ability of recombinant human keratinocyte growth factor (rHuKGF) to upregulate the expression of surfactant protein A (SP-A) and to downregulate pulmonary inflammation that occurs after allogeneic bone marrow transplantation (BMT). To establish a causal relationship, rHuKGF (5 mg/kg) was administered subcutaneously for three consecutive days before irradiation to SP-A-sufficient and -deficient [SP-A(+/+) and SP-A(-/-), respectively] mice given inflammation-inducing allogeneic spleen T cells at the time of BMT. In contrast with SP-A(+/+) mice, rHuKGF failed to suppress the high levels of TNF-α, IFN-γ, and nitric oxide contained in bronchoalveolar lavage fluids collected on day 7 after BMT from SP-A(-/-) mice. Early post-BMT weight loss was attenuated by rHuKGF in both SP-A(+/+) and SP-A(-/-) recipients. In the absence of supportive respiratory care, however, SP-A deficiency eventually abolished the ability of rHuKGF to prevent weight loss and to improve survival monitored for 1 mo after allogeneic BMT. In further experiments, the addition of cyclophosphamide (which is known to cause severe injury to the alveolar epithelium in donor T cell-recipient mice) to the conditioning regimen prevented rHuKGF-induced upregulation of SP-A and suppression of lung inflammation in both SP-A(+/+) and SP-A(-/-) mice. We conclude that endogenous baseline SP-A levels and optimal upregulation of SP-A are required for the anti-inflammatory protective effects of KGF after allogeneic transplantation.

Original languageEnglish (US)
Pages (from-to)L602-L610
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Issue number3 29-3
StatePublished - Sep 1 2003


  • Graft vs. host disease
  • Inflammation
  • Lung compliance
  • Macrophages
  • T lymphocytes


Dive into the research topics of 'Surfactant protein A is a required mediator of keratinocyte growth factor after experimental marrow transplantation'. Together they form a unique fingerprint.

Cite this