Direct Binding of Toll-Like Receptor 2 to Zymosan, and Zymosan-Induced NF-κB Activation and TNF-α Secretion Are Down-Regulated by Lung Collectin Surfactant Protein A

We have recently identified a toll-like receptor (TLR4)-interacting SPA4 peptide encoding amino acids: GDFRYSDGTPVNYTNWYRGE, a shorter region of human surfactant protein-A (SP-A).

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Cutting Edge: The Immunostimulatory Activity of the Lung Surfactant Protein-A Involves Toll-Like Receptor 4

The Journal of Immunology ◽

10.4049/jimmunol.168.12.5989 ◽

2002 ◽

Vol 168 (12) ◽

pp. 5989-5992 ◽

Cited By ~ 219

Author(s):

Loïc Guillot ◽

Viviane Balloy ◽

Francis X. McCormack ◽

Douglas T. Golenbock ◽

Michel Chignard ◽

...

Keyword(s):

Lung Surfactant ◽

Protein A ◽

Surfactant Protein ◽

Cutting Edge ◽

Surfactant Protein A ◽

Toll Like Receptor ◽

Immunostimulatory Activity ◽

Toll Like Receptor 4 ◽

Lung Surfactant Protein

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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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Pulmonary surfactant protein A and surfactant lipids upregulate IRAK-M, a negative regulator of TLR-mediated inflammation in human macrophages

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00067.2012 ◽

2012 ◽

Vol 303 (7) ◽

pp. L608-L616 ◽

Cited By ~ 40

Author(s):

Huy A. Nguyen ◽

Murugesan V. S. Rajaram ◽

Douglas A. Meyer ◽

Larry S. Schlesinger

Keyword(s):

Proinflammatory Cytokine ◽

Cytokine Production ◽

Protein A ◽

Surfactant Protein ◽

Negative Regulator ◽

Surfactant Protein A ◽

Proinflammatory Cytokine Production ◽

Human Macrophages ◽

Tnf Α

Alveolar macrophages (AMs) are exposed to frequent challenges from inhaled particulates and microbes and function as a first line of defense with a highly regulated immune response because of their unique biology as prototypic alternatively activated macrophages. Lung collectins, particularly surfactant protein A (SP-A), contribute to this activation state by fine-tuning the macrophage inflammatory response. During short-term (10 min–2 h) exposure, SP-A's regulation of human macrophage responses occurs through decreased activity of kinases required for proinflammatory cytokine production. However, AMs are continuously exposed to surfactant, and the biochemical pathways underlying long-term reduction of proinflammatory cytokine activity are not known. We investigated the molecular mechanism(s) underlying SP-A- and surfactant lipid-mediated suppression of proinflammatory cytokine production in response to Toll-like receptor (TLR) 4 (TLR4) activation over longer time periods. We found that exposure of human macrophages to SP-A for 6–24 h upregulates expression of IL-1 receptor-associated kinase M (IRAK-M), a negative regulator of TLR-mediated NF-κB activation. Exposure to Survanta, a natural bovine lung extract lacking SP-A, also enhances IRAK-M expression, but at lower magnitude and for a shorter duration than SP-A. Surfactant-mediated upregulation of IRAK-M in macrophages suppresses TLR4-mediated TNF-α and IL-6 production in response to LPS, and IRAK-M knockdown by small interfering RNA reverses this suppression. In contrast to TNF-α and IL-6, the surfactant components upregulate LPS-mediated immunoregulatory IL-10 production, an effect reversed by IRAK-M knockdown. In conclusion, these data identify an important signaling regulator in human macrophages that is used by surfactant to control the long-term alveolar inflammatory response, i.e., enhanced IRAK-M activity.

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