Asbestos-induced endothelial cell activation and injury. Demonstration of fiber phagocytosis and oxidant-dependent toxicity

Our plain-English summary of Asbestos-induced endothelial cell activation and injury. Demonstration of fiber phagocytosis and oxidant-dependent toxicity, by J.G. Garcia, L.D. Gray, R.F. Dodson, et al (The American Review of Respiratory Disease, 1988).

The study

• Authors: J.G. Garcia, L.D. Gray, R.F. Dodson, K.S. Callahan
• Journal: The American Review of Respiratory Disease
• Published: 1988;138(4):958-64
• Cited by: 32 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Vascular endothelial cell injury is important in the development of a variety of chronic interstitial lung disorders. However, the involvement of such injury in the inflammatory response associated with the inhalation of asbestos fibers is unclear and the mechanism of asbestos fiber cytotoxicity remains unknown. In the present study, human umbilical vein endothelial cells were challenged with amosite asbestos and several parameters of cellular function were examined. Electron microscopic examination revealed that endothelial cell exposure to asbestos resulted in active phagocytosis of these particulates. Biochemical evidence of dose-dependent asbestos-mediated endothelial cell activation was indicated by increased metabolism of arachidonic acid. For example, amosite asbestos (500 micrograms/ml) produced a ninefold increase in prostacyclin (PGI2) levels over those levels in non-exposed cells. Incubation of human endothelial cells with asbestos fibers induced specific 51Cr release in both a dose- and time-dependent fashion indicative of cellular injury. Injury induced by amosite asbestos was not significantly attenuated by treatment of the endothelial cell monolayer with either the iron chelator deferoxamine, which prevents hydroxyl radical (.OH) formation, or by the superoxide anion (O2-) scavenger, superoxide dismutase. However, significant dose-dependent protection was observed with the hydrogen peroxide (H2O2) scavenger, catalase. Chelation of elemental iron present within amosite asbestos fibers by deferoxamine produced a 33% reduction in asbestos cytotoxicity, suggesting a potential role for hydroxyl radical-mediated injury via the iron-catalyzed Haber-Weiss reaction.(ABSTRACT TRUNCATED AT 250 WORDS)

In plain English

In this laboratory cell-culture study, the authors exposed cultured endothelial cells (the cells that line blood vessels) from human umbilical cord veins to commercial-grade amosite asbestos, fiberglass or latex beads. Electron microscopy showed the cells actively engulfing asbestos, glass fibers and beads, with few signs of damage after 1 hour. Asbestos, and to a much lesser extent fiberglass, caused cell injury that increased over time. Injury was measured by release of a radioactive chromium label. Latex beads caused none. At 1 hour, asbestos at 500 and 250 micrograms per ml raised release of prostacyclin, a signalling substance, 8.7-fold and 5.2-fold. Fiberglass and beads did not raise it significantly. Catalase, which removes hydrogen peroxide, reduced asbestos injury in a dose-dependent way. Superoxide dismutase, and deferoxamine added to the cells, did not significantly reduce injury at 1 hour. Amosite stripped of iron with deferoxamine was less toxic. Iron-stripped amosite given with catalase cut injury by 87 plus or minus 3 percent compared with untreated amosite. The authors concluded that oxidants appear to be involved and that endothelial cells may take part in inflammation linked to asbestos inhalation.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: In vitro laboratory experiment on cultured human cells
• Who was studied: Human umbilical vein endothelial cells (HUVEC), cultured from umbilical cords obtained after normal delivery and used in first passage only. Research done at the University of Texas Health Center, Tyler, Texas. The number of cords is not stated.
• Exposure: Commercial-grade amosite asbestos (90% of fibers less than 0.5 micrometers in diameter and less than 10 micrometers long; average length 2.7 micrometers), at 25 to 500 micrograms per ml. Comparison materials were ground fiberglass of similar size and latex beads. Some cells were also given the oxidant scavengers catalase or superoxide dismutase, or the iron chelator deferoxamine. Iron-chelated amosite was also tested.
• Main results:
  • Scanning electron microscopy showed endothelial cells actively engulfing (phagocytosing) asbestos, fiberglass and latex beads.
  • Despite engulfing fibers, the cells showed few pathologic changes at 1 hour.
  • Asbestos, and to a much lesser extent fiberglass, caused chromium-51 release (cell injury) from the cell layers. Release increased with time from 30 minutes through 6 hours.
  • Latex beads caused no chromium-51 release at any time point.
  • At each concentration tested, asbestos caused significantly greater chromium-51 release than the same doses of fiberglass.
  • At 1 hour, asbestos significantly increased prostacyclin release: 8.7-fold at 500 micrograms per ml and 5.2-fold at 250 micrograms per ml, compared with unexposed cells. Fiberglass and latex beads did not significantly increase it.
  • Asbestos-induced injury was not significantly reduced when the cells were treated with deferoxamine (20 mM) or with superoxide dismutase (up to 600 U/ml), as measured at 1 hour. This refers to deferoxamine added to the cells, not to the separately tested iron-chelated fibers.
  • Catalase (a hydrogen peroxide scavenger) significantly reduced asbestos-induced cell injury, and its protection was dose dependent.
  • Catalase completely suppressed the asbestos-induced prostacyclin release.
  • Amosite that had been stripped of iron with deferoxamine was significantly less toxic to the cells than untreated amosite. The authors report a 33% reduction in cytotoxicity.
  • Catalase (3,000 U/ml) combined with deferoxamine-treated asbestos gave the greatest protection. Compared with untreated (native) asbestos, it reduced chromium-51 release by 87 plus or minus 3%.
  • Deferoxamine-treated asbestos produced significantly smaller increases in prostacyclin than untreated asbestos.
  • Indomethacin or aspirin (acetylsalicylic acid) did not prevent asbestos-induced cell injury, but did block the stimulated prostacyclin release.
• The authors' conclusion: The authors concluded that generation of oxidants, particularly hydrogen peroxide and hydroxyl radical, appears to be involved in asbestos toxicity to endothelial cells. They also concluded that vascular endothelial cells may be active participants in the inflammatory response associated with asbestos inhalation.
• Limitations the authors state:
  • The authors state that the exact mechanism by which asbestos is toxic to endothelium and alters its function is not entirely clear.
  • The authors state that a role for superoxide-mediated damage cannot be ruled out. Superoxide dismutase and catalase do not enter cells, so oxidants formed inside cells would not have been scavenged.

Topics

Medical terms in this study, explained in our Lexicon: Phagocytosis, Interstitial, Amosite, Hydroxyl Radical, Superoxide.

Related studies

• Vitronectin adsorption to chrysotile asbestos increases fiber phagocytosis and toxicity for mesothelial cells — J. Wu, W. Liu, et al. (2000)
• Scavengers of active oxygen species prevent cigarette smoke-induced asbestos fiber penetration in rat tracheal explants — A. Churg, J. Hobson, et al. (1989)
• Phagocytosis of chrysotile fibers by pleural mesothelial cells in culture — M.C. Jaurand, H. Kaplan, et al. (1979)
• Increased neutrophil adherence to endothelial cells exposed to asbestos — M.D. Treadwell, B.T. Mossman, et al. (1996)
• Microsomal lipid peroxidation and oxy-radicals formation are induced by insoluble iron-containing minerals — M. Fontecave, M. Jaouen, et al. (1990)
• Cellular ingestion, toxic effects, and lesions observed in human bronchial epithelial tissue and cells cultured with asbestos and glass fibers — A. Haugen, P.W. Schafer, et al. (1982)

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