Contrasting effects of alveolar macrophages and neutrophils on asbestos-induced pulmonary epithelial cell injury

Our plain-English summary of Contrasting effects of alveolar macrophages and neutrophils on asbestos-induced pulmonary epithelial cell injury, by D.W. Kamp, M.M. Dunn, J.S. Sbalchiero, et al (The American Journal of Physiology, 1994).

The study

• Authors: D.W. Kamp, M.M. Dunn, J.S. Sbalchiero, A.M. Knap, S.A. Weitzman
• Journal: The American Journal of Physiology
• Published: 1994;266(1 Pt 1):L84-91
• Cited by: 24 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Pulmonary toxicity from asbestos may be due in part to oxidant-mediated mechanisms. The purpose of this study was to determine whether alveolar macrophages (AM) contribute to asbestos-induced alveolar epithelial cell injury by oxidant-dependent mechanisms similar to that previously described for polymorphonuclear leukocytes (PMN). We assessed 51Cr release from cultured rat alveolar epithelial cells (RAEC) and transformed human pulmonary epithelial-like cell lines (rat L2 and human WI-26: HPEC). Amosite asbestos caused dose-dependent injury to both RAEC and L2 cells after an 18-h incubation period. Rat PMN increased asbestos-induced injury to RAEC (11 vs. 20% 51Cr release). In contrast, rat AM diminished asbestos-induced injury to RAEC and L2 cells by 60-80%. Human monocytes cultured for 72 h also attenuated asbestos-induced HPEC damage. Asbestos stimulated more H2O2 release from PMN than from AM isolated from the same rats (5.3 +/- 0.6 vs. 0.3 +/- 0.1 nmol x 10(6) cells-1 x 2h-1). The protective effect of rat AM, as opposed to PMN, was not due to differences in asbestos-induced toxicity to each cell type, since > 90% of AM and PMN were nonviable after 18 h. Transmission electron microscopy demonstrated comparable uptake of asbestos by AM and PMN after a 2-h incubation period. However, after an 18-h exposure period, the PMN were completely lysed, whereas over 90% of the AM contained fibers, despite morphologic evidence of cytotoxicity. These results demonstrate that AM, unlike PMN, can reduce alveolar epithelial cell injury in this model.(ABSTRACT TRUNCATED AT 250 WORDS)

In plain English

This laboratory study used cultured cells, not people or live animals. The authors exposed lung air-sac lining (alveolar epithelial) cells to amosite asbestos for 18 hours. These were rat cells grown from rat lungs, a rat cell line (L2) and a human cell line (WI-26). Damage was measured as release of a radioactive marker. Amosite damaged the rat cells more at higher doses. Adding rat neutrophils, a type of white blood cell, raised damage from 10.5% to 20.1% marker release. Adding rat alveolar macrophages lowered it to 4.2%. Macrophages also reduced damage to L2 cells, and cultured human monocytes reduced damage to the human cells. Asbestos made neutrophils release far more hydrogen peroxide than macrophages from the same rats. At the highest dose both cell types were almost all dead by 18 hours. Under the electron microscope, over 90% of macrophages still held fibers at 18 hours, while no intact neutrophils remained. The authors concluded that macrophages and neutrophils had opposite effects on asbestos-induced injury in this model. They noted the results cover only short-term exposure and may not reflect conditions in the body.

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 experiments
• Who was studied: Cultured cells. Rat alveolar epithelial cells: alveolar type II cells isolated from adult Harlan Sprague Dawley rats and cultured 7-10 days. A transformed rat pulmonary epithelial cell line (L2). A transformed human pulmonary epithelial-like cell line (WI-26). Added to these were rat neutrophils (PMN) from blood, rat alveolar macrophages (AM) obtained by lung lavage, and human blood monocytes cultured for 72 hours.
• Exposure: Amosite asbestos (UICC reference standard). Doses were 10 to 500 micrograms per milliliter for 18 hours. Fiber uptake was examined at 50 micrograms per milliliter for 2 or 18 hours.
• Main results:
  • Amosite caused dose-dependent injury to the cultured rat alveolar epithelial cells after 18 hours. The highest dose tested (500 micrograms per milliliter) caused 18.5 ± 2.4% marker (51Cr) release, p less than 0.01 vs. control, n = 27.
  • In the rat alveolar epithelial cells, asbestos alone (500 micrograms per milliliter) caused 10.5 ± 2.4% marker release. Adding rat neutrophils increased this to 20.1 ± 2.9%. Adding rat alveolar macrophages decreased it to 4.2 ± 1.2%. Both changes were p less than 0.05.
  • In rat L2 cells, asbestos (500 micrograms per milliliter) caused 20.5 ± 2.5% marker release. Rat macrophages reduced this to 13.8 ± 1.8% at a 2.5 to 1 macrophage-to-target cell ratio and to 5.6 ± 2.5% at a 5 to 1 ratio, p less than 0.01 vs. asbestos alone.
  • In the human WI-26 cells, human monocytes cultured for 72 hours reduced asbestos-induced damage from 26.0 ± 5.2% to 8.9 ± 4.0% marker release, p less than 0.005, n = 5.
  • After 18 hours at the highest asbestos dose, both macrophages and neutrophils had released about 91% of their total LDH (a marker of cell death). The authors concluded that the protective effect of macrophages was not explained by better survival.
  • Asbestos (500 micrograms per milliliter) raised hydrogen peroxide release from rat neutrophils to 5.3 ± 0.6 nmol per million cells per 2 hours, vs. 0.1 ± 0.1 without asbestos (n = 13, p less than 0.005). Release from rat macrophages from the same rats was 0.3 ± 0.1.
  • After 2 hours, both cell types had taken up fibers. Alveolar macrophages: 194 of 211 cells (92%), 9.3 fibers per cell. Neutrophils: 103 of 105 cells (98%), 12.9 fibers per cell.
  • After 18 hours, 31 of 34 macrophages (91%) still contained fibers, averaging 4.2 per cell, despite signs of cell injury. No intact neutrophils could be found.
• The authors' conclusion: The authors concluded that alveolar macrophages and neutrophils have distinct effects in modulating asbestos-induced alveolar epithelial cell injury in this model. Macrophages reduced the injury and neutrophils increased it. They suggested this may relate partly to lower hydrogen peroxide release and better fiber sequestration by macrophages, while stating that the precise mechanism remains unclear.
• Limitations the authors state:
  • The protective effect of macrophages relates only to epithelial cell survival. Macrophages also release factors that may contribute to fibrosis.
  • Mechanisms found in this laboratory model may not match conditions in the living body.
  • Conclusions are limited to short-term asbestos exposure. Macrophages may harm epithelial cells over longer periods, which could not be tested beyond 18 hours.

Topics

Medical terms in this study, explained in our Lexicon: Alveolar Macrophage, Amosite, Transmission Electron Microscopy (TEM).

Related studies

• Asbestos-induced injury to cultured human pulmonary epithelial-like cells: role of neutrophil elastase — D.W. Kamp, M. Dunne, et al. (1993)
• Bidirectional modulation of TNF-alpha production by alveolar macrophages in asbestos-induced pulmonary fibrosis — S. Ouellet, H. Yang, et al. (1993)
• Relative release of interleukin-1 beta and interleukin-1 receptor antagonist by alveolar macrophages. A study in asbestos-induced lung disease, sarcoidosis, and idiopathic pulmonary fibrosis — J.N. Kline, D.A. Schwartz, et al. (1993)
• Cigarette smoke augments asbestos-induced alveolar epithelial cell injury: role of free radicals — D.W. Kamp, M.J. Greenberger, et al. (1998)
• Lung mesothelial cell and fibroblast responses to pleural and alveolar macrophage supernatants and to lavage fluids from crocidolite-exposed rats — I.Y. Adamson, H. Prieditis, et al. (1997)
• Alveolar macrophage kinetics and multinucleated giant cell formation after lung injury — H. Prieditis, I.Y. Adamson (1996)

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