Increased neutrophil adherence to endothelial cells exposed to asbestos

Our plain-English summary of Increased neutrophil adherence to endothelial cells exposed to asbestos, by M.D. Treadwell, B.T. Mossman, A. Barchowsky (Toxicology and Applied Pharmacology, 1996).

The study

• Authors: M.D. Treadwell, B.T. Mossman, A. Barchowsky
• Journal: Toxicology and Applied Pharmacology
• Published: 1996;139(1):62-70
• Cited by: 15 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Inhalation of asbestos may activate the pulmonary endothelium to promote an inflammatory cell phenotype that participates in the development of pulmonary fibrosis. However, little is known about the effects of asbestos on endothelial cell function. Therefore, endothelial cells were exposed to chrysotile and crocidolite asbestos for up to 72 hr to investigate the effects of noncytotoxic concentrations of asbestos on cell function. Noncytolytic concentrations of chrysotile and crocidolite caused localized changes in cell morphology, resulting in activation of endothelial cells to a vacuolated, "spindle-shaped" morphology at sites of fiber deposition. The adherence of neutrophils (PMN) to control and asbestos-treated cultures was examined to determine the functional significance of this altered morphology. Chrysotile asbestos caused a time-dependent, 2- to 4-fold increase in PMN adherence that was localized to spindled endothelial cells in close contact with fibers. Monoclonal antibodies against intercellular adhesion molecule-1 (ICAM-1) inhibited this asbestos-induced PMN adherence. Solution hybridization demonstrated a 2.5-fold increase in steady-state levels of ICAM-1 mRNA in cells exposed to chrysotile asbestos for 8 hr. Exposure to crocidolite asbestos resulted in similar alteration in cell morphology and increase in PMN binding to endothelial cells, while a physically similar nonasbestos fiber, refractory ceramic fiber-1 did not cause morphologic change or increased PMN binding. These data suggest that asbestos fibers can specifically and directly activate endothelial cells, resulting in an activated cell morphology, increased ICAM-1 expression, and enhanced PMN adherence.

In plain English

This was a laboratory study of pig aortic endothelial cells (cells lining blood vessels) grown in culture. The cells were exposed to chrysotile asbestos, crocidolite asbestos, or a non-asbestos fiber, refractory ceramic fiber-1 (RCF-1). The researchers described the fiber amounts as noncytotoxic, meaning they did not significantly reduce cell metabolism or membrane integrity over 48 hours. With chrysotile at the amount printed as 10 mg/cm2, under 2% of cells lost membrane integrity by 48 hours. Cells touching chrysotile or crocidolite fibers took on an elongated, 'spindled' shape as early as 3 hours. RCF-1 did not change cell shape. Significantly more human neutrophils (white blood cells) stuck to the cells only after 4 to 8 hours of chrysotile exposure. After 24 hours of exposure, neutrophils stuck only to spindled cells next to chrysotile fibers. Crocidolite increased neutrophil binding 2.5-fold at 24 hours. RCF-1 gave no significant increase. ICAM-1 antibodies brought binding to chrysotile-exposed cells back to control levels. After chrysotile exposure, ICAM-1 messenger RNA peaked by 8 hours. The authors concluded that noncytotoxic asbestos concentrations directly activate endothelial cells.

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: laboratory cell-culture experiment (in vitro)
• Who was studied: First or second passage pig (porcine) aortic endothelial cells in culture, with freshly isolated human neutrophils (PMN) added to measure adherence
• Exposure: NIEHS reference chrysotile and crocidolite asbestos, and the non-asbestos refractory ceramic fiber-1 (RCF-1), for up to 72 hr. Typical concentrations were printed as 10 mg/cm2 chrysotile, 5 mg/cm2 crocidolite and 10 mg/cm2 RCF-1. These units may be scan-damaged; see text_problems.
• Main results:
  • The authors defined noncytotoxic as a fiber concentration that did not significantly decrease metabolic function or membrane integrity in the cultures over a 48-hr period
  • In cultures exposed to chrysotile (printed as 10 mg/cm2) for 48 hr, less than 2% of cells lost membrane integrity
  • Endothelial cells contacting chrysotile or crocidolite fibers became elongated as early as 3 hr after the fibers were added; RCF-1 did not change cell shape
  • Neutrophil adherence to chrysotile-exposed endothelial cells was significantly increased only after 4 to 8 hr of exposure
  • Endothelial cells exposed to crocidolite for 24 hr showed a 2.5-fold increase in neutrophil binding
  • RCF-1 did not significantly increase neutrophil binding
  • Myeloperoxidase activity, a measure of bound neutrophils, was 14.7 plus or minus 6.9 mOD/min with chrysotile, compared with 1.4 plus or minus 1.3 in controls (p less than 0.001)
  • In an experiment after 24 hr of asbestos exposure, neutrophils bound only to spindled endothelial cells next to chrysotile fibers
  • Antibodies to ICAM-1 (clones LB-2 and 15.2) significantly reduced asbestos-induced neutrophil adherence to control levels in chrysotile-exposed cells. Inhibition by an antibody to e-selectin was highly variable.
  • Chrysotile exposure produced a progressive increase in ICAM-1 mRNA, which was maximal by 8 hr
• The authors' conclusion: The authors concluded that noncytotoxic concentrations of asbestos directly activate endothelial cells, producing a spindled shape and increased neutrophil adherence through ICAM-1. Because RCF-1 had no such effect, they suggested the activation is specific to asbestos and is not a mechanical response to any fiber.

Topics

Medical terms in this study, explained in our Lexicon: Pulmonary Fibrosis, Chrysotile, Crocidolite, Deposition, Monoclonal.

Related studies

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• Contrasting effects of alveolar macrophages and neutrophils on asbestos-induced pulmonary epithelial cell injury — D.W. Kamp, M.M. Dunn, et al. (1994)
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• Neutrophil chemotactic factor release and neutrophil alveolitis in asbestos-exposed individuals — A.A. Hayes, A.H. Rose, et al. (1988)

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