IL-8 response of cyclically stretching alveolar epithelial cells exposed to non-fibrous particles

Our plain-English summary of IL-8 response of cyclically stretching alveolar epithelial cells exposed to non-fibrous particles, by S.M. Mijailovich, K. Hamada, A. Tsuda (Annals of Biomedical Engineering, 2007).

The study

• Authors: S.M. Mijailovich, K. Hamada, A. Tsuda
• Journal: Annals of Biomedical Engineering
• Published: 2007;35(4):582-94
• Cited by: 5 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Using a cell stretcher device, we have previously shown that A549 cells exposed to asbestos fibers gave significantly increased cytokine responses (IL-8) when they were cyclically stretched [Tsuda, A., B. K. Stringer, S. M. Mijailovich, R. A. Rogers, K. Hamada, and M. L. Gray. Am. J. Respir. Cell Mol. Biol. 21(4):455-462, 1999]. In the present study, cell stretching experiments were performed using non-fibrous riebeckite particles, instead of fibrous particles. Riebeckite particles are ground asbestos fibers with the size of a few microns and non-fibrous shape, and are often used as "non-toxic" control particles in the studies of fibrous particle-induced pathogenesis. Although it is generally assumed that riebeckite particles do not elicit strong biological responses, in our studies in cyclically stretched cell cultures, the riebeckite particles coated with adhesion proteins induced significant IL-8 responses, but in static cell cultures the treatment with adhesion protein-coated riebeckite did not induce comparable cytokine responses. To interpret these data, we have developed a simple mathematical model of adhesive interactions between a cell layer and rigid fibrous/non-fibrous particles that were subjected to external tensile forces. The analysis showed that because of considerable dissimilarity in deformations (i.e., strain mismatch) between the cells and particles during breathing, the attachment of particles as small as 1 micro in size could induce significant mechanical forces on the cell surface receptors, which may trigger subsequent adverse cell response under dynamic stretching conditions.

In plain English

This was a laboratory cell study plus a mathematical model. The authors grew A549 cells, a human alveolar epithelial tumor cell line, on a stretchable membrane. They exposed the cells to riebeckite particles, which are crocidolite asbestos fibers ground into non-fibrous particles a few microns in size and often used as "non-toxic" controls. The particles were coated with the adhesion protein fibronectin and given at 5 µg/cm2. Some cultures were stretched by 5% at 10 cycles per minute for 6 hours to mimic breathing; others were kept still. The authors then measured IL-8, an inflammatory signaling protein. Particles without stretching, and stretching without particles, did not raise IL-8 above background levels. Particles combined with stretching significantly increased IL-8 (p less than 0.04; n = 5 for particle-treated and n = 3 for no-particle cultures). In the model, receptor forces rose sharply within 0.5 µm of particle edges. The authors suggested that particles 1 µm or longer could generate appreciably high forces under stretching. The authors concluded that non-fibrous riebeckite can induce IL-8 secretion by these cells under dynamic conditions. Uncoated particles were not tested.

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 (in vitro) cell culture experiment comparing stretched and static cultures, plus a mathematical model of the forces between cells and attached particles
• Who was studied: Human alveolar epithelial tumor cell line A549 grown in culture. There were n = 5 fibronectin-coated riebeckite cultures and n = 3 no-particle cultures, each tested static and cyclically stretched.
• Exposure: Riebeckite particles (ground from crocidolite asbestos fibers, non-fibrous, a few microns in size) coated with fibronectin, at 250 µg/plate (5 µg/cm2). Cultures were either cyclically stretched at 5% strain and 10 cycles per minute for 6 hours, or left static.
• Main results:
  • In static cultures, riebeckite particle treatment without stretching did not raise IL-8 above background levels.
  • Stretching cells that received no particles did not raise IL-8 above background level either.
  • Combining riebeckite particle treatment with cyclic stretching significantly increased IL-8 production by A549 cells (p less than 0.04, ANOVA).
  • Cell viability was generally greater than 90%.
  • In the mathematical model (particles 0.5, 1, 3 and 5 µm long, 5% strain), receptor force rose sharply near particle edges regardless of particle size, typically within 0.5 µm of the edge.
  • In the model, for particles longer than 1 µm, the maximum receptor force at the particle tip may exceed the receptor detachment force. The authors used 10 pN only as a reference value for bond breaking.
  • The authors suggested that particles 1 µm or longer could generate appreciably high receptor forces under dynamic stretching conditions.
• The authors' conclusion: The authors concluded that riebeckite particles, although non-fibrous, can induce IL-8 secretion by A549 cells under dynamic (stretching) conditions. They proposed that mechanical force on cell-surface receptors at particle edges may trigger adverse cell responses.
• Limitations the authors state:
  • Experiments with uncoated particles were not included.
  • The model did not account for the ruffled shape of real cell membranes.
  • It was unclear whether the calculated maximum receptor force is above or below the force that breaks receptor bonds.
  • Whether stretching affects particle uptake by cells was not addressed.

Topics

Medical terms in this study, explained in our Lexicon: A549 Cells, Cytokine, Riebeckite.

Related studies

• Alveolar cell stretching in the presence of fibrous particles induces interleukin-8 responses — A. Tsuda, B.K. Stringer, et al. (1999)
• Mitochondria-targeted Ogg1 and aconitase-2 prevent oxidant-induced mitochondrial DNA damage in alveolar epithelial cells — S.J. Kim, P. Cheresh, et al. (2014)
• Changes in DNA 8-hydroxyguanine levels, 8-hydroxyguanine repair activity, and hOGG1 and hMTH1 mRNA expression in human lung alveolar epithelial cells induced by crocidolite asbestos — H.N. Kim, Y. Morimoto, et al. (2001)
• Mitochondrial catalase overexpressed transgenic mice are protected against lung fibrosis in part via preventing alveolar epithelial cell mitochondrial DNA damage — S.J. Kim, P. Cheresh, et al. (2016)
• Asbestos causes apoptosis in alveolar epithelial cells: role of iron-induced free radicals — A. Aljandali, H. Pollack, et al. (2001)
• P53 mediates amosite asbestos-induced alveolar epithelial cell mitochondria-regulated apoptosis — V. Panduri, S. Surapureddi, et al. (2006)

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