Selective differences in macrophage populations and monokine production in resolving pulmonary granuloma and fibrosis

Our plain-English summary of Selective differences in macrophage populations and monokine production in resolving pulmonary granuloma and fibrosis, by I. Lemaire (The American Journal of Pathology, 1991).

The study

• Author: I. Lemaire
• Journal: The American Journal of Pathology
• Published: 1991;138(2):487-95
• Cited by: 32 articles, as counted by NIH iCite
• Read it: PubMed · Free full text

Abstract

Alveolar macrophages (AM) and their production of interleukin-1-like activity (IL-1) and macrophage-derived growth factor for fibroblasts (MDGF) were examined during chronic inflammatory reactions leading to either granuloma formation or fibrosis. Groups of five rats each received, respectively, a single transtracheal injection of xonotlite, attapulgite, short chrysotile 4T30, UICC chrysotile B asbestos, or saline. One month later, such treatments induced either no change (xonotlite), granuloma formation (attapulgite and short chrysotile 4T30), or fibrosis (UICC chrysotile B). By 8 months, however, the granulomatous reactions had resolved or greatly diminished, whereas the fibrosis persisted irreversibly. Parallel examination of cell populations obtained by bronchoalveolar lavage revealed that multinucleated giant macrophages (MGC) were present in lavage fluids of animals with resolving granulomatous reactions but absent in those obtained from animals with lung fibrosis. Evaluation of monokine production by inflammatory macrophages also revealed significant differences. Enhanced production of IL-1-like activity was seen in both types of lung injury, although especially during the early stage (1 month) and decreased thereafter (8 months). By contrast, augmentation of MDGF production was observed in animals with lung fibrosis only and persisted up to 9 months. Taken together, these data indicate that production of selected cytokines, as well as AM differentiation along a given pathway, may modulate the outcome of a chronic inflammatory response.

In plain English

This was an animal experiment in male Wistar rats. Rats received one windpipe injection of saline, UICC chrysotile B asbestos, very short chrysotile 4T30, attapulgite clay, or xonotlite (a calcium silicate). Doses were 1 to 10 mg, with chrysotile B results reported at 1 and 5 mg. In total, 130 animals were examined at 1 and 8 months. At 1 month, chrysotile B caused severe fibrosis, 4T30 and attapulgite caused granulomas, and xonotlite caused no significant change. By 8 months, 4T30 granulomas had resolved or decreased and attapulgite granulomas had decreased; the author cited earlier and unpublished work showing chrysotile B fibrosis persisting. At 1 month, lung washings from attapulgite- and 4T30-treated rats held significant numbers of multinucleated giant macrophages; chrysotile B numbers did not differ significantly from controls. Only macrophages from chrysotile B-treated rats showed raised activity of macrophage-derived growth factor for fibroblasts (MDGF) at 1 month. Stimulated interleukin-1-like activity rose with the three lesion-causing fibers at 1 month. By 8 months, the 4T30 increase was no longer apparent and the attapulgite one was much smaller. The author concluded that macrophage types and products may influence how inflammation ends.

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: animal experiment (rat model of lung inflammation and fibrosis)
• Who was studied: Male Wistar rats weighing 250 to 300 g from Charles River Canada, in groups of five per dose. A total of 130 animals were examined by bronchoalveolar lavage 1 and 8 months after treatment.
• Exposure: A single transtracheal injection of one of the following: saline; UICC chrysotile B (58% of fibers shorter than 5 micrometers); very short chrysotile 4T30 (100% shorter than 5 micrometers); attapulgite (100% shorter than 1 micrometer); or xonotlite (100% shorter than 3 micrometers). Doses were 1, 5 or 10 mg. Results for UICC chrysotile B are reported at 1 and 5 mg.
• Main results:
  • At 1 month, UICC chrysotile B (1 and 5 mg) caused severe fibrotic lesions, mainly around the small airways. Short 4T30 chrysotile and attapulgite caused granulomatous reactions. Xonotlite caused no significant change.
  • By 8 months, granulomas from short 4T30 chrysotile (5 and 10 mg) had resolved or decreased. Granulomas from attapulgite (5 and 10 mg) had decreased significantly in number and size.
  • Fibrosis from UICC chrysotile B was reported to persist up to 6 months (an earlier study) and up to 9 months (unpublished data).
  • At 1 month, neutrophils in lung washings made up 6% of total cells in attapulgite-treated rats and 1.6% in chrysotile B-treated rats (5 mg). In controls they made up 0.1%.
  • At 1 month, a significant number of multinucleated giant macrophages were found in lung washings of all animals given attapulgite or 4T30 chrysotile (5 mg).
  • The number of multinucleated giant macrophages in chrysotile B- and xonotlite-treated rats was not significantly different from controls.
  • At 1 month, macrophages from rats given 4T30 chrysotile, attapulgite or xonotlite did not produce more fibroblast-stimulating activity than controls. Only macrophages from UICC chrysotile B-treated rats showed higher production of macrophage-derived growth factor for fibroblasts (MDGF).
  • At 1 month, stimulated (MDP) interleukin-1-like activity from macrophages increased 47 times with attapulgite, 57 times with chrysotile B and 3.9 times with 4T30.
  • By 8 months, the small increase in interleukin-1-like activity seen with 4T30 fibers was no longer apparent.
  • At 8 months, stimulated interleukin-1-like activity was still significantly higher in attapulgite-treated rats (two times control), but much lower than at 1 month.
• The authors' conclusion: The author concluded that the nature of alveolar macrophage populations and their monokine production may influence the outcome of inflammatory reactions.
• Limitations the authors state:
  • The author stated that other mechanisms for the decline in interleukin-1-like activity, such as regulation by other cytokines or inhibitory factors, could not be ruled out.

Topics

Medical terms in this study, explained in our Lexicon: Macrophage, Granuloma, Fibrosis, Alveolar Macrophage, Fibroblast, Palygorskite (Attapulgite), Chrysotile, UICC.

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