SP-A and TLR4 localization in lung tissue of SM-exposed patients

Int Immunopharmacol. 2020 Mar:80:105936. doi: 10.1016/j.intimp.2019.105936. Epub 2019 Nov 11.

Abstract

Introduction: Long-term pulmonary complications are one of the major long-term consequences of sulfur mustard (SM) exposure. Toll-like receptor 4 (TLR4) involves in the pathogenesis of several pulmonary disorders. Surfactant protein-A (SP-A) regulates LPS-induced TLR4 localization and activation responses. However, the intensity and significance of TLR4 and SP-A expression by lung cells in SM-exposed patients is not clear.

Methods: The gene expression of TLR4 (through real-time PCR) and TLR4 and SP-A positive cells and alveolar type II cells, as SP-A producers, (using IHC) were assessed in formalin fixed paraffin embedded (FFPE) specimens from SM-exposed (n = 17), and non-SM exposed individuals (n = 12).

Results: TLR4 gene expression did not change between study groups. However, its cell surface presentation was significantly reduced in SM-exposed patients and particularly in which with constrictive bronchiolitis compared with the control group (P < 0.001 and P = 0.002, respectively). Frequency of alveolar type II cells was lower in the case group rather than the control group while the number of SP-A positive cells did not alter.

Conclusions: These findings suggest that reduced TLR4 cell surface presentation may have anti-inflammatory function and SP-A may have a critical role in regulation of inflammatory responses in SM-exposed patients. Further investigation on other possible mechanisms involved in TLR4 internalization maybe help to illustrate the modulatory or inflammatory activity of TLR4 in these patients.

Keywords: Alveolar type II cells; Constrictive bronchiolitis; Mustard gas; Surfactant protein-A (SP-A); Toll-like receptor 4 (TLR4).

MeSH terms

  • Adult
  • Alveolar Epithelial Cells / immunology
  • Alveolar Epithelial Cells / pathology*
  • Bronchiolitis Obliterans / chemically induced*
  • Bronchiolitis Obliterans / drug therapy
  • Bronchiolitis Obliterans / immunology
  • Bronchiolitis Obliterans / pathology
  • Case-Control Studies
  • Chemical Warfare Agents / toxicity*
  • Gene Expression Profiling
  • Humans
  • Immunohistochemistry
  • Iran
  • Male
  • Middle Aged
  • Mustard Gas / toxicity*
  • Pulmonary Surfactant-Associated Protein A / analysis
  • Pulmonary Surfactant-Associated Protein A / metabolism*
  • Time Factors
  • Toll-Like Receptor 4 / analysis
  • Toll-Like Receptor 4 / metabolism*

Substances

  • Chemical Warfare Agents
  • Pulmonary Surfactant-Associated Protein A
  • SFTPA1 protein, human
  • TLR4 protein, human
  • Toll-Like Receptor 4
  • Mustard Gas