Combined SP-A-bleomycin effect on cytokines by THP-1 cells: impact of surfactant lipids on this effect

Huang, Weixiong; Wang, Guirong; Phelps, David S.; Al‐Mondhiry, Hamid; Floros, Joanna

doi:10.1152/ajplung.00434.2001

Cited by 25 publications

(24 citation statements)

References 44 publications

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“…21 A substantial amount of evidence accrued from in vitro and in vivo studies using animals or patients has shown that bleomycin upregulates expression of TNF-a, IL-1b and TGF-b pro-inflammatory proteins. 22,23 These cytokines are produced by endothelial cells, alveolar macrophages, lymphocytes, neutrophils and fibroblasts. The role of these cytokines in inflammation, edema formation, fibrosis and tissue remodeling has been well-documented.…”

Section: Discussionmentioning

confidence: 99%

Erythropoietin ameliorates chemotherapy‐induced fibrosis of the lungs in a preclinical murine model

Sigounas

Salleng

Mehlhop

et al. 2008

Intl Journal of Cancer

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Organ toxicity induced by chemotherapeutic drugs is a serious obstacle in the effective treatment of patients suffering from cancer and autoimmune disease. A strong association exists between pulmonary toxicity, particularly fibrosis, and chemotherapeutic drugs. Attempts have been made to identify compounds capable of suppressing fibrosis. In addition to its erythropoietic activity, erythropoietin (EPO) has been shown to have effects on nonhemopoietic cells. Therefore, we postulated that EPO may exert beneficial effects on lung tissue during chemotherapy. To test our hypothesis, we investigated pulmonary changes caused by bleomycin, a fibrosis‐inducing agent, in animals treated with the drug alone and in combination with EPO. Fibrosis, cellular alterations and structural changes were assayed by blind analysis of the lung sections. A 6‐fold decrease in the number of prominent endothelial cells—suspected to be indicative of cellular activation and inflammatory response—was observed in lung sections derived from mice treated with bleomycin and EPO compared to animals injected with bleomycin alone (p < 0.008). Additionally, there was twice the number of ICAM1‐positive endothelial cells in animals treated with bleomycin alone compared with the number in the bleomycin and EPO‐treated group (p < 0.05). Alveolar mononuclear phagocytic hyperplasia was reduced by as much as 100% in animals treated with bleomycin and EPO compared to animals treated with bleomycin alone (p < 0.03). Finally, a 5‐fold decrease in interstitial fibrosis was observed in lung sections obtained from animals treated with bleomycin and EPO (p < 0.02). We conclude that EPO can ameliorate drug‐induced fibrosis and endothelial damage caused by chemotherapeutic agents. © 2008 Wiley‐Liss, Inc.

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Section: Discussionmentioning

confidence: 99%

Erythropoietin ameliorates chemotherapy‐induced fibrosis of the lungs in a preclinical murine model

Sigounas

Salleng

Mehlhop

et al. 2008

Intl Journal of Cancer

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“…SP-A was purified by butanol extraction from the bronchoalveolar lavage (BAL) fluid of alveolar proteinosis patients (13) as described previously (20). The purified protein was examined by two-dimensional gel electrophoresis and silver staining and was found to be Ͼ99% pure.…”

Section: Methodsmentioning

confidence: 99%

Surfactant protein A increases matrix metalloproteinase-9 production by THP-1 cells

Lara

Umstead

Davis

et al. 2003

American Journal of Physiology-Lung Cellular and Molecular Phys

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trix metalloproteinase (MMP)-9 from alveolar macrophages is a major source of elastolytic activity in the lung. It is increased in the bronchoalveolar lavage fluid of patients with emphysema. Although the importance of macrophage-derived elastolytic activity in the pathogenesis of emphysema is well established, questions remain about MMP-9 regulation and activity. Because surfactant protein A (SP-A) is capable of modulating other functions of human monocytic cells, we hypothesized that SP-A may regulate MMP-9 expression. Vitamin D 3-differentiated THP-1 cells and peripheral blood mononuclear cells were stimulated in vitro with several concentrations of SP-A for different incubation times. MMP-9 mRNA expression was measured by dot-blot analysis, gelatinolytic activity in the medium was determined by gel zymography, protein expression was determined by ELISA, and a specific MMP-9 activity assay was used to measure the state of activation of this enzyme in the cell supernatants. SP-A induced the expression of MMP-9 in both cell types, the effect was time and dose dependent, and MMP-9 was released in its zymogen form. On the basis of results of neutralizing antibody studies, we believe that SP-A action is mediated through Toll-like receptor-2. Even though the biological meaning of these findings remains to be elucidated, these observations suggest the presence of a novel, locally controlled mechanism by which MMP-9 levels may be regulated in alveolar macrophages. We speculate that SP-A may influence the protease/antiprotease balance in the lungs of patients with quantitative and/or qualitative changes in surfactant constituents favoring an abnormal breakdown of extracellular matrix components. gelatinase; macrophage; chronic obstructive pulmonary disease

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“…SP-A was purified (16) from the BAL fluid obtained from a patient with AP (AP BAL hSP-A) as described previously (19). The concentration of SP-A was determined using the Micro BCA Protein Assay (Pierce, Rockford, IL) using RNase A as a standard, and the purity of the SP-A preparation was verified by 2-D-PAGE followed by silver staining.…”

Section: Purification Of Sp-a From Human Balmentioning

confidence: 99%

Impact of ozone exposure on the phagocytic activity of human surfactant protein A (SP-A) and SP-A variants

Mikerov¹,

Umstead²,

Gan³

et al. 2008

American Journal of Physiology-Lung Cellular and Molecular Phys

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118

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Surfactant protein A (SP-A) enhances phagocytosis of Pseudomonas aeruginosa. SP-A1 and SP-A2 encode human (h) SP-A; SP-A2 products enhance phagocytosis more than SP-A1. Oxidation can affect SP-A function. We hypothesized that in vivo and in vitro ozone-induced oxidation of SP-A (as assessed by its carbonylation level) negatively affects its function in phagocytosis (as assessed by bacteria cell association). To test this, we used P. aeruginosa, rat alveolar macrophages (AMs), hSP-As with varying levels of in vivo (natural) oxidation, and ozone-exposed SP-A2 (1A, 1A 0 ) and SP-A1 (6A 2 , 6A 4 ) variants. SP-A oxidation levels (carbonylation) were measured; AMs were incubated with bacteria in the presence of SP-A, and the phagocytic index was calculated. We found: 1) the phagocytic activity of hSP-A is reduced with increasing levels of in vivo SP-A carbonylation; 2) in vitro ozone exposure of hSP-A decreases its function in a dose-dependent manner as well as its ability to enhance phagocytosis of either gram-negative or gram-positive bacteria; 3) the activity of both SP-A1 and SP-A2 decreases in response to in vitro ozone exposure of proteins with SP-A2 being affected more than SP-A1. We conclude that both in vivo and in vitro oxidative modifications of SP-A by carbonylation reduce its ability to enhance phagocytosis of bacteria and that the activity of SP-A2 is affected more by in vitro ozone-induced oxidation. We speculate that functional differences between SP-A1 and SP-A2 exist in vivo and that the redox status of the lung microenvironment differentially affects function of SP-A1 and SP-

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Combined SP-A-bleomycin effect on cytokines by THP-1 cells: impact of surfactant lipids on this effect

Cited by 25 publications

References 44 publications

Erythropoietin ameliorates chemotherapy‐induced fibrosis of the lungs in a preclinical murine model

Erythropoietin ameliorates chemotherapy‐induced fibrosis of the lungs in a preclinical murine model

Surfactant protein A increases matrix metalloproteinase-9 production by THP-1 cells

Impact of ozone exposure on the phagocytic activity of human surfactant protein A (SP-A) and SP-A variants

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