Effect of Surfactant Protein a (Sp-A) on the Production of Cytokines by Human Pulmonary Macrophages

Arias-Dı́az, Javier; García-Verdugo, Ignacio; Casals, Cristina; Sanchez-Rico, Natalia; Vara, Elena; Balibrea, J.L.

doi:10.1097/00024382-200014030-00010

Cited by 41 publications

(36 citation statements)

References 25 publications

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“…We observed a significant reduction, but not a complete elimination, of TNF-␣ secretion when macrophages were pretreated with SP-A and then treated with either the TLR4 ligand, LPS, or the TLR2 ligand Pam 3 Cys. Our TLR4 data are consistent with previous publications that showed that SP-A decreases TNF-␣ secretion in the presence of LPS (28,(72)(73)(74). Overall, these data provide further evidence for the role of SP-A in dampening the proinflammatory response in the lung environment.…”

Section: Discussionsupporting

confidence: 92%

Pulmonary Surfactant Protein A Regulates TLR Expression and Activity in Human Macrophages

Henning

Azad²,

Parsa

et al. 2008

The Journal of Immunology

134

115

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The pulmonary innate immune system responds to various airborne microbes. Although its specificity is broad and based on the recognition of pathogen-associated molecular patterns, it is uniquely regulated to limit inflammation and thereby prevent damage to the gas-exchanging alveoli. Macrophages, critical cell determinants of this system, recognize microbes through pattern recognition receptors such as TLRs, which typically mediate proinflammatory responses. The lung collectin, surfactant protein A (SP-A), has emerged as an important innate immune determinant that regulates microbe-macrophage interactions in this environment. In this study, we report the basal and SP-A-induced transcriptional and posttranslational regulation of TLR2 and TLR4 expression during the differentiation of primary human monocytes into macrophages. Despite SP-A’s ability to up-regulate TLR2 expression on human macrophages, it dampens TLR2 and TLR4 signaling in these cells. SP-A decreases the phosphorylation of IκBα, a key regulator of NF-κB activity, and nuclear translocation of p65 which result in diminished TNF-α secretion in response to TLR ligands. SP-A also reduces the phosphorylation of TLR signaling proteins upstream of NF-κB, including members of the MAPK family. Finally, we report for the first time that SP-A decreases the phosphorylation of Akt, a major cell regulator of NF-κB and potentially MAPKs. These data identify a critical role for SP-A in modulating the lung inflammatory response by regulating macrophage TLR activity.

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Section: Discussionsupporting

confidence: 92%

Pulmonary Surfactant Protein A Regulates TLR Expression and Activity in Human Macrophages

Henning

Azad²,

Parsa

et al. 2008

The Journal of Immunology

134

115

View full text Add to dashboard Cite

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“…Surfactant modulates several inflammatory processes including cell proliferation and the release of inflammatory mediators. The lipid components of surfactant appear to have predominantly immunosuppressive effects, but the hydrophilic surfactant protein, SP-A, has been reported to exhibit both immunostimulatory and immunosuppressive activity (25). Thus, in vitro studies by McIntosh et al (5) and Sano et al (6) suggest that SP-A can inhibit LPS-induced TNF-␣ production by alveolar macrophages.…”

Section: Discussionmentioning

confidence: 99%

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

Guillot

Balloy

McCormack

et al. 2002

The Journal of Immunology

289

164

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The collectin surfactant protein-A (SP-A) is involved in the innate host defense and the regulation of inflammatory processes in the lung. In this work we investigated the molecular mechanisms related to the immunostimulatory activity of SP-A using macrophages from C3H/HeJ mice, which carry an inactivating mutation in the Toll-like receptor (TLR)4 gene, and TLR4-transfected Chinese hamster ovary cells. We demonstrate that SP-A-induced activation of the NF-κB signaling pathway and up-regulation of cytokine synthesis such as TNF-α and IL-10 are critically dependent on the TLR4 functional complex. These findings support the concept that TLR4 is a pattern recognition receptor that signals in response to both foreign pathogens and endogenous host mediators.

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“…In vitro studies conducted on the direct effects of lung collectins on alveolar macrophages have been somewhat controversial because they found both stimulation [27][28][29][30] and inhibition 27,[31][32][33] of proinflammatory functions, including TNF-α production. 34 Only a few studies described the effects of SP-A and SP-D on dendritic cell function.…”

Section: Tnf; Sp-d; Dendritic Cell; Mouse Model; Airway Inflammationmentioning

confidence: 99%

Surfactant protein D inhibits TNF-α production by macrophages and dendritic cells in mice

Hortobagyi

Kierstein

Krytska

et al. 2008

Journal of Allergy and Clinical Immunology

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Effect of Surfactant Protein a (Sp-A) on the Production of Cytokines by Human Pulmonary Macrophages

Cited by 41 publications

References 25 publications

Pulmonary Surfactant Protein A Regulates TLR Expression and Activity in Human Macrophages

Pulmonary Surfactant Protein A Regulates TLR Expression and Activity in Human Macrophages

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

Surfactant protein D inhibits TNF-α production by macrophages and dendritic cells in mice

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