Surfactant protein A regulates cytokine production in the monocytic cell line THP-1

Kremlev, Sergey G.; Umstead, Todd M.; Phelps, David S.

doi:10.1152/ajplung.1997.272.5.l996

Cited by 66 publications

(68 citation statements)

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“…Surfactant protein A (SP-A), a 34-to 36-kDa glycoprotein, plays a major role in the modulation of innate host defense in the lung (7,16,21,41,48,52). SP-A has been shown to stimulate chemotaxis of macrophages (70), enhance phagocytosis (11,34,44,46,47,50,63), induce generation of reactive oxidants (61), regulate the nitric oxide production (1,23), and influence the proliferation of immune cells (2,38) and the production of proinflammatory cytokines (3,27,37,39,68,69). SP-A can bind to receptors on the macrophage membrane (35).…”

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confidence: 99%

SP-A1 and SP-A2 variants differentially enhance association ofPseudomonas aeruginosawith rat alveolar macrophages

Mikerov¹,

Umstead²,

Huang³

et al. 2005

American Journal of Physiology-Lung Cellular and Molecular Phys

128

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aeruginosa. Two genes, SP-A1 and SP-A2, encode human SP-A. We hypothesized that genetically determined differences in the activity of SP-A1 and SP-A2 gene products exist. To test this, we studied association of a nonmucoid P. aeruginosa strain (ATCC 39018) with rat alveolar macrophages in the presence or absence of insect cellexpressed human SP-A variants. We used two trios, each consisting of SP-A1, SP-A2, and their coexpressed SP-A1/SP-A2 variants. We tested the 6A 2 and 6A 4 alleles (for SP-A1), the 1A 0 and 1A alleles (for SP-A2), and their respective coexpressed SP-A1/SP-A2 gene products. After incubation of alveolar macrophages with P. aeruginosa in the presence of the SP-A variants at 37°C for 1 h, the cell association of bacteria was assessed by light microscopy analysis. We found 1) depending on SP-A concentration and variant, SP-A2 variants significantly increased the cell association more than the SP-A1 variants (the phagocytic index for SP-A1 was ϳ52-95% of the SP-A2 activity); 2) coexpressed variants at certain concentrations were more active than single gene products; and 3) the phagocytic index for SP-A variants was ϳ18 -41% of the human SP-A from bronchoalveolar lavage. We conclude that human SP-A variants in vitro enhance association of P. aeruginosa with rat alveolar macrophages differentially and in a concentration-dependent manner, with SP-A2 variants having a higher activity compared with SP-A1 variants.

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confidence: 99%

SP-A1 and SP-A2 variants differentially enhance association ofPseudomonas aeruginosawith rat alveolar macrophages

Mikerov¹,

Umstead²,

Huang³

et al. 2005

American Journal of Physiology-Lung Cellular and Molecular Phys

128

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“…Human SP-A from bronchoalveolar lavage (BAL) can stimulate cytokine production in the macrophage-like cell line, THP-1, and this effect is inhibited by the surfactant lipids (14,15). SP-A variants expressed in vitro using the baculovirus-mediated expression system stimulate TNF-α production in THP-1 cells.…”

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confidence: 99%

The effect of ozone exposure on the ability of human surfactant protein a variants to stimulate cytokine production.

Wang

Umstead

Phelps

et al. 2002

Environ Health Perspect

126

197

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Ozone exposure can cause inflammation and impaired lung function. Human surfactant protein A (SP-A) may play a role in inflammation by modulating cytokine production by macrophages. SP-A is encoded by two genes, SP-A1 and SP-A2, and several allelic variants have been characterized for each gene. These allelic variants differ among themselves in amino acids that may exhibit differential sensitivity to ozone-induced oxidation and this may produce functional differences. We studied the effects of SP-A variants before and after ozone exposure on the production of tumor necrosis factor (TNF)-alpha and interleukin (IL)-8. These are important proinflammatory cytokines and are expressed by the macrophage-like THP-1 cells. Eight variants were expressed in vitro, characterized by gel electrophoresis, and studied. These included six single-gene SP-A alleles and two SP-A variants derived from both genes. Variants were exposed to ozone at 1 ppm for 4 hr at 37 degrees C, and we compared their ability to stimulate cytokine (TNF-alpha and IL-8) production by THP-1 cells to air-exposed and unexposed SP-A variants. We found that a) SP-A2 variants (1A, 1A(0), 1A(1) stimulate significantly more TNF-alpha and IL-8 production than SP-A1 variants (6A, 6A(2), 6A(4); b) coexpressed SP-A variants (1A(0)/6A(2), 1A(1)/6A(4) have significantly higher activity than single gene products; c) after ozone exposure, all SP-A variants showed a decreased ability to stimulate TNF-alpha and IL-8 production, and the level of the decrease varied among SP-A variants (26-48%); and d) human SP-A from patients with alveolar proteinosis exhibited a minimal decrease (18% and 12%, respectively) in its ability to stimulate TNF-alpha and IL-8 after in vitro ozone exposure. We conclude that biochemical and functional differences exist among SP-A variants, that ozone exposure modulates the ability of SP-A variants to stimulate cytokines by THP-1 cells, and that SP-As from bronchoalveolar lavage (BAL) fluid of certain alveolar proteinosis patients may be oxidized in vivo.

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“…Previous studies have demonstrated that SP-A exhibits stimulatory, as well as inhibitory, effects on alveolar macrophages and cells of the monocyte/macrophage lineage. Stimulatory effects of SP-A on these cells include increased oxidative activity (30,34,72,83), increased production of proinflammatory cytokines (43,44), increased expression of cell surface proteins (42), increased matrix metalloproteinase production (79), enhanced chemotaxis in part via directed actin polymerization (76), and enhanced phagocytosis (21a, 48, 75, 84). Inhibitory effects of SP-A include decreased cytokine expression and nitric oxide production in mouse and rat macrophages pretreated with LPS (3,11,51).…”

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confidence: 99%

“…Using the in vitro O 3 exposure system, we studied the effects of O 3 on lung defense mechanisms by exposing THP-1 cells (a model for alveolar macrophages) to O 3 . Previous work has shown that the THP-1 cell line is a suitable model for such study (4,82,83) and that human SP-A enhances the expression of proinflammatory cytokines and cell surface proteins in THP-1 cells (42,44). Moreover, the ability of recombinant SP-A variants to stimulate cytokine production by THP-1 cells has been shown to be reduced following O 3 exposure of the variants (34,83).…”

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confidence: 99%

Modulatory effects of ozone on THP-1 cells in response to SP-A stimulation

Janic

Umstead

Phelps

et al. 2005

American Journal of Physiology-Lung Cellular and Molecular Phys

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, a major component of air pollution and a strong oxidizing agent, can lead to lung injury associated with edema, inflammation, and epithelial cell damage. The effects of O 3 on pulmonary immune cells have been studied in various in vivo and in vitro systems. We have shown previously that O 3 exposure of surfactant protein (SP)-A decreases its ability to modulate proinflammatory cytokine production by cells of monocyte/macrophage lineage (THP-1 cells). In this report, we exposed THP-1 cells and/or native SP-A obtained from bronchoalveolar lavage of patients with alveolar proteinosis to O 3 and studied cytokine production and NF-B signaling. The results showed 1) exposure of THP-1 cells to O 3 significantly decreased their ability to express TNF-␣ in response to SP-A; TNF-␣ production, under these conditions, was still significantly higher than basal (unstimulated) levels in filtered air-exposed THP-1 cells; 2) exposure of both THP-1 cells and SP-A to O 3 did not result in any significant differences in TNF-␣ expression compared with basal levels; 3) O 3 exposure of SP-A resulted in a decreased ability of SP-A to activate the NF-B pathway, as assessed by the lack of significant increase and decrease of the nuclear p65 subunit of NF-B and cytoplasmic I B␣, respectively; and 4) O 3 exposure of THP-1 cells resulted in a decrease in SP-A-mediated THP-1 cell responsiveness, which did not seem to be mediated via the classic NF-B pathway. These findings indicate that O 3 exposure may mediate its effect on macrophage function both directly and indirectly (via SP-A oxidation) and by involving different mechanisms.inflammation; tumor necrosis factor-␣; nuclear factor-B; I B␣; surfactant protein A OZONE (O 3 ) IS A MAJOR COMPONENT of photochemical air pollution. Approximately 113 million people live in areas with O 3 levels above the National Ambient Air Quality (NAAQ) standards for the daily exposure limit, noted as a maximum of 0.12 ppm for 1 h or 0.08 ppm cumulative for 8 consecutive hours (1). O 3 is a strong oxidizing agent that can be rapidly converted into a number of reactive oxygen species (ROS). O 3 exposure has been associated with impaired lung function (53) and with the majority of pathological changes localized in the lower airways. Due to its very low water solubility, O 3 cannot effectively penetrate through the thick epithelial lining fluid in the upper airways. However, the thinner lining in the lower airways allows O 3 to interact with various elements of the fluid and the underlying cells.O 3 and other oxidants exhibit their toxicity by reacting with cell proteins and lipids. This interaction often results in edema, inflammation, and epithelial cell damage causing lung injury and surfactant derangement (66, 67). Furthermore, both morphological (6, 7) and biochemical (26, 27) changes in surfactant are observed following O 3 exposure. An extensive body of work has been generated by various groups to support the hypothesis that O 3 -induced changes lead to a compromised immune response in the lung. However,...

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Surfactant protein A regulates cytokine production in the monocytic cell line THP-1

Cited by 66 publications

References 0 publications

SP-A1 and SP-A2 variants differentially enhance association ofPseudomonas aeruginosawith rat alveolar macrophages

SP-A1 and SP-A2 variants differentially enhance association ofPseudomonas aeruginosawith rat alveolar macrophages

The effect of ozone exposure on the ability of human surfactant protein a variants to stimulate cytokine production.

Modulatory effects of ozone on THP-1 cells in response to SP-A stimulation

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