Cytokines and particle-induced inflammatory cell recruitment

Our plain-English summary of Cytokines and particle-induced inflammatory cell recruitment, by K.E. Driscoll, J.M. Carter, D.G. Hassenbein, et al (Environmental Health Perspectives, 1997).

The study

• Authors: K.E. Driscoll, J.M. Carter, D.G. Hassenbein, B. Howard
• Journal: Environmental Health Perspectives
• Published: 1997;105 Suppl 5(Suppl 5):1159-64
• Type of article: Review
• Cited by: 156 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

The inflammatory response is a key component of host defense. However, excessive or persistent inflammation can contribute to the pathogenesis of disease. Inflammation is regulated, in part, by cytokines, which are small, typically glycosylated proteins that interact with membrane receptors to regulate cellular processes such as proliferation, differentiation, and secretion. During the past 10 years studies in humans and experimental animals have demonstrated that a cytokine called tumor necrosis factor alpha (TNF-alpha) plays a key role in the initiation of inflammatory responses in the lung and other tissues, including inflammation resulting from inhalation of noxious particles. There is now compelling evidence that one of the pathways by which inhaled particles stimulate the recruitment and subsequent activation of inflammatory cells is through the activation of lung macrophages to release TNF-alpha. TNF-alpha then acts via paracrine and autocrine pathways to stimulate cells to release other cytokines known as chemokines, which are directly chemotactic to leukocytes and other cells that participate in inflammatory and wound healing responses. In addition to a TNF-alpha-mediated pathway, there is growing evidence that some particles such as quartz and crocidolite can directly activate lung epithelial cells to release chemokines such as macrophage inflammatory protein-2, cytokine-induced neutrophil chemoattractant, and interleukin-8. A direct stimulatory effect of particles on lung epithelium may represent an additional or alternate pathway by which inhaled particles may elicit inflammation in the lung. Recent studies have suggested that oxidative stress may be a component of the mechanism by which particles activate cytokine production in cells such as macrophages and epithelial cells. The contribution of oxidative stress to particle-induced cytokine gene expression appears to be mediated, at least in part, through activation of the transcription factor nuclear factor kappa B.

In plain English

This conference paper reviewed evidence on how inhaled particles trigger inflammatory cell recruitment in the lung, including data from the authors' own laboratory. The authors summarised in vitro findings that quartz, crocidolite and chrysotile activated rat and human alveolar macrophages to release tumor necrosis factor alpha (TNF-alpha). Titanium dioxide, aluminum oxide and latex beads gave no response in rat macrophages, and titanium dioxide gave an equivocal response in human macrophages. In rats, pretreatment with an antibody to TNF-alpha significantly reduced neutrophil numbers in bronchoalveolar lavage fluid after quartz inhalation (p less than 0.01). Pretreatment with anti-MIP-2 antiserum gave an approximately 60% reduction in the neutrophil response to instilled quartz (p less than 0.05). In rat alveolar epithelial cells (RLE-6TN), quartz increased MIP-2 and CINC mRNA in a dose-related way without detectable TNF-alpha. Crocidolite also increased MIP-2 mRNA, whereas titanium dioxide and MMVF10 glass fibers did not. In these cells the oxygen radical scavenger TMTU attenuated quartz-induced MIP-2 gene expression. In results the authors called preliminary, TMTU also attenuated quartz-induced nuclear NF-kappa B translocation.

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: Narrative review/conference paper summarising published evidence, incorporating the authors' own rat in vivo and rat lung epithelial cell in vitro experiments
• Who was studied: Experimental animals and cells: F344 rats (groups of six, three per pretreatment exposed), the rat alveolar type II cell line RLE-6TN and primary rat alveolar type II cells. The reviewed studies also covered human alveolar macrophages, the human A549 lung carcinoma line and human volunteers
• Exposure: Mineral and other particles: quartz (silica), crocidolite and chrysotile asbestos, titanium dioxide, MMVF10 glass fibers, wollastonite, aluminum oxide, latex beads, coal dust, carbon black and endotoxin. In vivo doses were quartz at 100 mg/m3 for 6 hr by inhalation or 5 mg/kg by intratracheal instillation; the in vitro dose was quartz at 20 µg/cm2
• Main results:
  • In rats exposed to quartz aerosol, pretreatment with anti-TNF-alpha IgG significantly reduced the increase in bronchoalveolar lavage fluid neutrophils compared with nonimmune antibody controls (p less than 0.01)
  • In rats given 5 mg/kg quartz intratracheally, passive immunization with rabbit anti-MIP-2 serum produced an approximate 60% reduction in the neutrophil inflammatory response (p less than 0.05 versus the other quartz-treated groups)
  • In RLE-6TN rat lung epithelial cells, in vitro quartz increased MIP-2 and CINC mRNA in an apparently dose-related way, and this was also seen in primary rat alveolar type II cells. Nuclear runoff analysis showed increased MIP-2 gene transcription, and no TNF-alpha was detected in the cultures
  • In RLE-6TN cells, crocidolite asbestos increased MIP-2 mRNA expression, whereas titanium dioxide and MMVF10 glass fibers did not
  • Adding the oxygen radical scavenger TMTU to RLE-6TN cells attenuated quartz-induced MIP-2 gene expression, and DMSO, ethanol and mannitol had a similar effect. In results described as preliminary, TMTU also attenuated quartz-induced nuclear translocation of NF-kappa B
  • The reviewed in vitro data (Table 1) rated alveolar macrophage TNF-alpha responses as +++ for quartz, crocidolite and chrysotile in both rat and human macrophages, and ++ for coal dust in human macrophages. Titanium dioxide gave no response in rat macrophages and an equivocal (+/-) response in human macrophages. Aluminum oxide and latex beads gave no response and were tested in rat macrophages only
• The authors' conclusion: The authors concluded that TNF-alpha released by alveolar macrophages plays a critical role in particle-induced inflammatory cell recruitment through a chemokine network. They also concluded that particles can directly activate lung epithelial cells to produce chemokines, as an additional or alternate pathway, and that particle-induced oxidative stress, acting partly through NF-kappa B, may influence cytokine expression
• Limitations the authors state:
  • The authors described the TMTU and NF-kappa B translocation findings (Figure 6B) as preliminary
  • The authors stated that the mechanisms by which particle-induced oxidative stress activates cytokine gene expression are not known
  • The authors stated that the signaling mechanisms leading to NF-kappa B nuclear translocation had not been determined

Topics

Medical terms in this study, explained in our Lexicon: Cytokine, Inflammation, Necrosis, Macrophage, Crocidolite, Epithelium, Oxidative Stress, Nuclear Factor kappa B (NF-κB).

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