Surfactant Protein A Decreases Lung Injury and Mortality after Murine Marrow Transplantation

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.

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The Significance of KL-6 as Prognosis Monitoring Biomarker in Patients With Severe COVID-19 From Stabilized Stage Toward Convalescence

10.21203/rs.3.rs-191056/v1 ◽

2021 ◽

Author(s):

Long He ◽

Liu Lu ◽

Ming Zong ◽

Huang Zhou ◽

Lan Wang ◽

...

Keyword(s):

Lung Injury ◽

Protein A ◽

Alveolar Epithelium ◽

Surfactant Protein ◽

Surfactant Protein A ◽

Monocyte Count ◽

Type Ii ◽

Tnf Α ◽

Ifn Γ ◽

Blood Routine

Abstract Background: This study aims to identify some biomarkers for monitoring the recovery of lung injury in severe COVID-19 patients from stabilized stage toward convalescence.Methods: We enrolled participants who diagnosed with severe COVID-19 (n = 28) and health volunteers (n = 25) from Taikang Tongji (Wuhan) Hospital. The patients were in a stabilized stage and had a course of 48.1±12.8 days. We followed these patients for 90 days. The blood routine, cytokines (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p70, IL-17A, TNF-α, IFN-α, IFN-γ), type II alveolar epithelium injury indicators (Surfactant protein A (SP-A), Krebs von den Lungen-6 (KL-6)) and chest CT were tested on the 1, 30, 60, and 90 days after enrollment. Results: In stabilized stage, the parameters of blood routine and some cytokines (IL-1β, IL-2, IL-4, IL-12p70, TNF-α) had bounced back to normal (p>0.05). Some cytokines (IL-5, IL-6, IL-10, IL-17A, IFN-α, IFN-γ) and type II alveolar epithelium injury indicators (SP-A and KL-6) were still higher than normal (p<0.05). During the stabilized stage to convalescence, in spite of the variation of monocyte count, monocyte/lymphocyte ratio, IL-5, IL-10, IL-12p70, IL-17A, IFN-γ, IFN-α, SP-A and KL-6 were downward trend (p<0.05), only KL-6 level (p<0.05) could simultaneously reflect the lung injury volume which be measured by CT. Conclusions: Our preliminary data indicated that KL-6 could be an effective prognostic biomarker for monitoring the recovery of lung function in patients with severe COVID-19 from stabilized stage toward convalescence.

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Surfactant Protein-A Nanobody-Conjugated Liposomes Loaded With Methylprednisolone for Lung Targeting and Therapeutic Effect for Acute Lung Injury

CHEST Journal ◽

10.1016/j.chest.2016.02.473 ◽

2016 ◽

Vol 149 (4) ◽

pp. A454

Author(s):

Huiping Li

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Therapeutic Effect ◽

Protein A ◽

Surfactant Protein ◽

Surfactant Protein A ◽

Lung Targeting

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Enhanced Lung Injury and Delayed Clearance of Pneumocystis carinii in Surfactant Protein A-Deficient Mice: Attenuation of Cytokine Responses and Reactive Oxygen-Nitrogen Species

Infection and Immunity ◽

10.1128/iai.72.10.6002-6011.2004 ◽

2004 ◽

Vol 72 (10) ◽

pp. 6002-6011 ◽

Cited By ~ 46

Author(s):

Elena N. Atochina ◽

James M. Beck ◽

Angela M. Preston ◽

Angela Haczku ◽

Yaniv Tomer ◽

...

Keyword(s):

Lung Injury ◽

Pneumocystis Carinii ◽

Protein A ◽

Reactive Oxygen ◽

Surfactant Protein ◽

Surfactant Protein A ◽

Interleukin 4 ◽

Nitrogen Species ◽

Cell Counts ◽

Deficient Mice

ABSTRACT Surfactant protein A (SP-A), a member of the collectin family, selectively binds to Pneumocystis carinii and mediates interactions between pathogen and host alveolar macrophages in vitro. To test the hypothesis that mice lacking SP-A have delayed clearance of Pneumocystis organisms and enhanced lung injury, wild-type C57BL/6 (WT) and SP-A-deficient mice (SP-A−/−) with or without selective CD4+-T-cell depletion were intratracheally inoculated with Pneumocystis organisms. Four weeks later, CD4-depleted SP-A-deficient mice had developed a more severe Pneumocystis infection than CD4-depleted WT (P. carinii pneumonia [PCP] scores of 3 versus 2, respectively). Whereas all non-CD4-depleted WT mice were free of PCP, intact SP-A−/− mice also had evidence of increased organism burden. Pneumocystis infection in SP-A-deficient mice was associated histologically with enhanced peribronchial and/or perivascular cellularity (score of 4 versus 2, SP-A−/− versus C57BL/6 mice, respectively) and a corresponding increase in bronchoalveolar lavage (BAL) cell counts. Increases in SP-D content, gamma interferon, interleukin-4, interleukin-5, and tumor necrosis factor alpha in BAL fluid occurred but were attenuated in PCP-infected SP-A−/− mice compared to WT mice. There were increases in total BAL NO levels in both infected groups, but nitrite levels were higher in SP-A−/− mice, indicating a reduction in production of higher oxides of nitrogen that was also reflected in lower levels of 3-nitrotyrosine staining in the SP-A−/− group. We conclude that despite increases in inflammatory cells, SP-A-deficient mice infected with P. carinii exhibit an enhanced susceptibility to the organism and attenuated production of proinflammatory cytokines and reactive oxygen-nitrogen species. These data support the concept that SP-A is a local effector molecule in the lung host defense against P. carinii in vivo.

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