Simultaneous absence of surfactant proteins A and D increases lung inflammation and injury after allogeneic HSCT in mice.
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.
Gram
Kendra
K
Banner Children's Hospital, Mesa, AZ 85202, USA.
Yang
Shuxia
S
Steiner
Marie
M
Somani
Arif
A
Hawgood
Samuel
S
Blazar
Bruce R
BR
Panoskaltsis-Mortari
Angela
A
Haddad
Imad Y
IY
D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology; D001992:Bronchoalveolar Lavage Fluid; D018932:Chemokine CCL2 / Q000378:metabolism; D003520:Cyclophosphamide / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D007124:Immunoenzyme Techniques; D007371:Interferon-gamma / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009566:Nitrates / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D011014:Pneumonia / Q000209:etiology* / Q000378:metabolism / Q000628:therapy; D037662:Pulmonary Surfactant-Associated Protein A / Q000502:physiology*; D037663:Pulmonary Surfactant-Associated Protein D / Q000502:physiology*; D012129:Respiratory Function Tests; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014916:Whole-Body Irradiation
D018906:Antineoplastic Agents, Alkylating; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D009566:Nitrates; D009573:Nitrites; D037662:Pulmonary Surfactant-Associated Protein A; D037663:Pulmonary Surfactant-Associated Protein D; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D003520:Cyclophosphamide