Pulmonary macrophages are attracted to inhaled particles through complement activation

Our plain-English summary of Pulmonary macrophages are attracted to inhaled particles through complement activation, by D.B. Warheit, L.H. Overby, G. George, et al (Experimental Lung Research, 1988).

The study

• Authors: D.B. Warheit, L.H. Overby, G. George, A.R. Brody
• Journal: Experimental Lung Research
• Published: 1988;14(1):51-66
• Cited by: 68 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Pulmonary macrophages play a central role in clearing inhaled particles from the lung. Previously, we showed that inhaled asbestos fibers activate complement-dependent chemotactic factors on alveolar surfaces to facilitate macrophage recruitment to sites of fiber deposition. In the studies presented here, we have tested a variety of inorganic particles for complement activation in vitro and correlated these data with results on particle-induced macrophage accumulation in vivo. We found that significant chemotactic activity was activated in rat serum and concentrated lavaged proteins by chrysotile and crocidolite asbestos, iron-coated chrysotile asbestos, fiberglass, and wollastonite fibers, as well as by carbonyl iron and zymosan particles. Ash from the Mt. St. Helens volcano did not induce chemotactic activity in either the serum or lavaged proteins. Rats were exposed to brief aerosols of each of the particles listed above (except zymosan). All the particle types studied were deposited primarily at first alveolar duct bifurcations. In addition, all of the particles, except Mt. St. Helens ash, induced at 48 h postexposure significant accumulations of macrophages at these sites. Time-course studies of carbonyl iron particle exposure demonstrated that iron induced a rapid macrophage response, but both particles and phagocytic macrophages were cleared from alveolar surfaces within 8 days after exposure. The Mt. St. Helens ash induced no macrophage accumulation at any time postexposure. We conclude that particles with a wide variety of physical characteristics are capable of activating complement and consequently attracting macrophages, both in vitro and in vivo. We suggest that complement activation is a mechanism through which pulmonary macrophages can detect inhaled particles on alveolar surfaces.

In plain English

This was a laboratory and animal study. The authors tested whether inorganic particles activate complement, a group of proteins in blood and lung fluid, and so produce signals that attract the lung's scavenger cells, called pulmonary macrophages. Rat serum was mixed with chrysotile asbestos, crocidolite asbestos, iron-treated chrysotile, glass fibers, wollastonite fibers, carbonyl iron, zymosan (a known complement activator) or volcanic ash from Mt. St. Helens (a negative control). Proteins washed from rat lungs were mixed with the same materials except glass fibers. Male rats breathed the same dusts, except zymosan, for 1, 3 or 5 hours. Every particle except the ash increased macrophage attraction in serum. Every particle tested in lung fluid, apart from the ash, also did so there. All the inhaled particles settled mainly where the small air ducts first branch. By 48 hours, every dust except the ash had drawn macrophages to 85-99% of these sites. The ash drew no significant numbers within 8 days. The authors concluded that particles with widely varying physical characteristics can activate complement and so attract macrophages.

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) study of complement activation, measured by how strongly rat lung macrophages migrated toward particle-treated serum or lung-wash proteins, combined with a short-term inhalation experiment in rats
• Who was studied: Male CD(SD)BR rats (Charles River), 8-10 weeks old, plus serum, lung-wash fluid and macrophages taken from rats. The number of rats in the inhalation experiments is not stated. The serum chemotaxis table reports N = 9 for each particle tested.
• Exposure: The materials were chrysotile asbestos (Jeffrey Mine, Quebec), UICC crocidolite asbestos, chrysotile treated with ammonium ferrous sulfate (iron-treated), code 100 glass fibers, carbonyl iron powder, wollastonite (NYAD G) and Mt. St. Helens volcanic ash (negative control). Zymosan was a positive control used in vitro only. In the test-tube experiments, dusts were mixed with serum at 25 mg/ml (zymosan at 10 mg/ml). Lung-wash proteins were tested with all of these except fiberglass. Rats inhaled aerosols at 10 to 20 mg/m3 total mass for 1, 3 or 5 hours. Control rats were sham-exposed to room air.
• Main results:
  • In rat serum, chrysotile, iron-treated chrysotile, crocidolite, zymosan, fiberglass, carbonyl iron and wollastonite each produced a greater macrophage migration response than serum incubated with Mt. St. Helens ash.
  • A checkerboard test indicated that the response was directed migration toward the signal (chemotaxis), not just increased random movement.
  • Fiberglass was not included in the lung-wash protein experiments. In cell-free lung-wash proteins, carbonyl iron, wollastonite, chrysotile, iron-treated chrysotile, crocidolite and zymosan increased chemotactic activity. The figure legend reports p less than 0.01 compared with ash-treated or decomplemented controls. Removing complement beforehand abolished this activity. Mt. St. Helens ash did not activate complement in lung fluid.
  • In rats, all the inhaled particles, whatever their shape or chemical makeup, were deposited mainly at alveolar duct bifurcations.
  • By 48 hours after exposure, every dust except the ash had led to macrophages gathering at 85-99% of first alveolar duct bifurcations. Data for crocidolite were described but not shown.
  • In rats exposed for 1 or 3 hours, Mt. St. Helens ash did not cause significant macrophage gathering within 8 days, even though about as many ash particles were deposited as with the other dusts.
  • In carbonyl iron-exposed rats, macrophages responded quickly. The disappearance of iron particles from the bifurcations matched the percentage of macrophages that had engulfed particles. Both the particles and these macrophages were cleared within 8 days.
  • A test for bacterial endotoxin found no bacterial contamination on any of the particles.
• The authors' conclusion: The authors concluded that particles with a wide variety of physical characteristics can activate complement and consequently attract macrophages, both in vitro and in vivo. They suggested that complement activation, probably through a factor called C5a, is a way lung macrophages detect inhaled particles.

Mines named here

Asbestos mines this study is about. Each mine's page says who ran it, when it worked, and what it produced.

• Jeffrey mine, Asbestos, Quebec

All asbestos mines

Topics

The National Library of Medicine indexes this study under subjects our site covers: Chrysotile, Crocidolite.

Medical terms in this study, explained in our Lexicon: Macrophage, Deposition, Chrysotile, Crocidolite, Wollastonite.

Related studies

• Relative effects of asbestos and wollastonite on alveolar macrophages — W.H. Pailes, D.J. Judy, et al. (1984)
• Measurement of reactive oxygen metabolites produced by human monocyte-derived macrophages exposed to mineral dusts — P. Nyberg, M. Klockars (1990)
• Time course of chemotactic factor generation and the corresponding macrophage response to asbestos inhalation — D.B. Warheit, L.H. Hill, et al. (1986)
• Cytotoxicity of respirable dusts from industrial minerals: comparison of two naturally occurring and two man-made silicates — D. Nadeau, L. Fouquette-Couture, et al. (1987)
• Wollastonite fibers in vitro generate reactive oxygen species able to lyse erythrocytes and activate the complement alternate pathway — M. Governa, L. Camilucci, et al. (1998)
• Sialic acid mediates the initial binding of positively charged inorganic particles to alveolar macrophage membranes — J.E. Gallagher, G. George, et al. (1987)

Browse more research in Experimental Lung Research, or return to medical research.