Surfactant Protein A Inhibits Peptidoglycan-induced Tumor Necrosis Factor-α Secretion in U937 Cells and Alveolar Macrophages by Direct Interaction with Toll-like Receptor 2

Murakami, Seiji; Iwaki, Daisuke; Mitsuzawa, Hiroaki; Sano, Hitomi; Takahashi, Hiroki; Voelker, Dennis R.; Akino, Toyoaki; Kuroki, Yoshio

doi:10.1074/jbc.m106671200

Cited by 162 publications

(143 citation statements)

References 55 publications

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“…44 In brief, glycosylated and deglycosylated sTLR4 proteins (2 mg) were electrophoresed on a 13% polyacrylamide gel in The binding of MBL to sTLR4 was also examined using microtiter wells. sTLR4 or HSA (10 mg/ml, 50 ml/well) was coated onto microtiter wells, which were then incubated with 10 mM Hepes buffer (pH 7.4) containing 0.15 M NaCl, 5 mM CaCl 2 and 5 mg/ml bovine serum albumin (buffer C) to block nonspecific binding.…”

Section: Analyses Of Binding Of Mbl To Stlr4mentioning

confidence: 99%

Mannan-binding lectin directly interacts with Toll-like receptor 4 and suppresses lipopolysaccharide-induced inflammatory cytokine secretion from THP-1 cells

et al. 2011

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Mannan-binding lectin (MBL) plays a key role in the lectin pathway of complement activation and can influence cytokine expression. Toll-like receptor 4 (TLR4) is expressed extensively and has been demonstrated to be involved in lipopolysaccharide (LPS)-induced signaling. We first sought to determine whether MBL exposure could modulate LPS-induced inflammatory cytokine secretion and nuclear factor-kB (NF-kB) activity by using the monocytoid cell line THP-1. We then investigated the possible mechanisms underlying any observed regulatory effect. Using ELISA and reverse transcriptase polymerase chain reaction (RT-PCR) analysis, we found that at both the protein and mRNA levels, treatment with MBL suppresses LPS-induced tumor-necrosis factor (TNF)-a and IL-12 production in THP-1 cells. An electrophoretic mobility shift assay and western blot analysis revealed that MBL treatment can inhibit LPS-induced NF-kB DNA binding and translocation in THP-1 cells. While the binding of MBL to THP-1 cells was evident at physiological calcium concentrations, this binding occurred optimally in response to supraphysiological calcium concentrations. This binding can be partly inhibited by treatment with either a soluble form of recombinant TLR4 extracellular domain or anti-TLR4 monoclonal antibody (HTA125). Activation of THP-1 cells by LPS treatment resulted in increased MBL binding. We also observed that MBL could directly bind to the extracellular domain of TLR4 in a dose-dependent manner, and this interaction could attenuate the binding of LPS to cell surfaces. Taken together, these data suggest that MBL may affect cytokine expression through modulation of LPS-/TLR-signaling pathways. These findings suggest that MBL may play an important role in both immune regulation and the signaling pathways involved in cytokine networks.

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Section: Analyses Of Binding Of Mbl To Stlr4mentioning

confidence: 99%

Mannan-binding lectin directly interacts with Toll-like receptor 4 and suppresses lipopolysaccharide-induced inflammatory cytokine secretion from THP-1 cells

et al. 2011

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“…When sTLR2 or sCD14 was incubated without iPGN, none of them was sedimentable. When surfactant protein A, which does not bind to iPGN (34), was used as a negative control, iPGN failed to cosediment this protein.…”

Section: Recombinantmentioning

confidence: 99%

The Extracellular Toll-like Receptor 2 Domain Directly Binds Peptidoglycan Derived from Staphylococcus aureus

Iwaki

Mitsuzawa

Murakami

et al. 2002

Journal of Biological Chemistry

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162

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Toll-like receptor 2 (TLR2) has been recognized to mediate cell signaling in response to peptidoglycan (PGN), a major cell wall component of Gram-positive bacteria. The mechanism by which TLR2 recognizes PGN is unknown. It is not even clear whether TLR2 directly binds to PGN. In this study, we generated a soluble form of recombinant TLR2 (sTLR2) possessing only its putative extracellular domain by using the baculovirus expression system to examine the direct interaction between sTLR2 and PGN. sTLR2 bound avidly to insoluble PGN (iPGN) from Staphylococcus aureus coated onto microtiter wells in a concentration-dependent manner. In contrast, sTLR2 exhibited a very weak binding to lipopolysaccharide. iPGN cosedimented sTLR2 after the mixture of iPGN and sTLR2 had been incubated and centrifuged. sTLR2 partially attenuated the iPGN-induced NF-B activation in TLR2-transfected HEK 293 cells and the iPGN-induced IL-8 secretion in U937 cells. One of anti-human TLR2 monoclonal antibodies, which blocked iPGN-induced NF-B activation in TLR2-transfected cells, inhibited the binding of sTLR2 to iPGN. In addition, we found that sCD14 interacted with sTLR2 and increased the binding of sTLR2 to iPGN. From these results, we conclude that the extracellular TLR2 domain directly binds to PGN.

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“…In the last few years, we have demonstrated that SP-A interacts with the pattern recognition receptors CD14 and Toll-like receptor (TLR)-2, and modulates the immune response to bacterial components [7][8][9]. The binding of SP-A to TLR4 is under investigation.…”

Section: Discussionmentioning

confidence: 99%

“…SP-A has been reported to bind to various spectra of microorganisms and enhance phagocytosis by alveolar macrophages [5,6]. SP-A also modulates the cellular responses to microorganisms via its direct interactions with the pattern recognition receptors [7][8][9]. Animals lacking SP-A exhibit reduced bacterial clearance and elevated pulmonary inflammation in response to microbial challenge [10][11][12].…”

Section: Introductionmentioning

confidence: 99%

Lactoferrin and surfactant protein A exhibit distinct binding specificity to F protein and differently modulate respiratory syncytial virus infection

et al. 2003

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Surfactant protein A (SP-A) and lactoferrin (LF) play important roles in innate immune systems in the respiratory mucous membranes. We investigated how SP-A and LF act against respiratory syncytial virus (RSV) infection. The present study indicated that RSV-induced IL-8 secretion from HEp-2 cells was up-regulated by SP-A (170% of control) but downregulated by LF (23% of control). RSV infectivity determined by viral titers and the uptake of FITC-labeled RSV were also increased by SP-A, but decreased by LF. To clarify the mechanism of these opposite effects, we examined the interactions of SP-A and LF with RSV F protein, the most important surface glycoprotein for viral penetration. RSV F protein was found to be the ligand for both SP-A and LF, but the manners of binding were different. LF directly interacted with the F 1 subunit, which involved antigenic sites of F protein. Contrarily, SP-A associated with the F 2 subunit, which was highly glycosylated. SP-A but not LF failed to interact with deglycosylated F protein. Moreover, SP-A initiated the hemolyzing fusion activity of F protein. These results suggest that SP-A and LF modulate RSV infection by different binding specificity to F protein.

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Surfactant Protein A Inhibits Peptidoglycan-induced Tumor Necrosis Factor-α Secretion in U937 Cells and Alveolar Macrophages by Direct Interaction with Toll-like Receptor 2

Abstract: Pulmonary surfactant protein A (SP-A

Cited by 162 publications

References 55 publications

Mannan-binding lectin directly interacts with Toll-like receptor 4 and suppresses lipopolysaccharide-induced inflammatory cytokine secretion from THP-1 cells

Mannan-binding lectin directly interacts with Toll-like receptor 4 and suppresses lipopolysaccharide-induced inflammatory cytokine secretion from THP-1 cells

The Extracellular Toll-like Receptor 2 Domain Directly Binds Peptidoglycan Derived from Staphylococcus aureus

Lactoferrin and surfactant protein A exhibit distinct binding specificity to F protein and differently modulate respiratory syncytial virus infection

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