Human Innate Immune Responses to Hexamethylene Diisocyanate (HDI) and HDI-Albumin Conjugates

Details

• Personal Author:
  Liu J ; Liu Q ; Redlich CA ; Wisnewski AV
• Description:
  BACKGROUND: Isocyanates, a leading cause of occupational asthma, are known to induce adaptive immune responses; however, innate immune responses, which generally precede and regulate adaptive immunity, remain largely uncharacterized. OBJECTIVE: The aim of the study was to identify and characterize the cellular, molecular and systemic innate immune responses induced by hexamethylene diisocyanate (HDI). METHODS: Human peripheral blood mononuclear cells (PBMCs) were stimulated in vitro with HDI-albumin conjugates or control antigen, and changes in phenotype, gene and protein expression were characterized by flow cytometry, microarray, Western blot and ELISA. Cell uptake of isocyanate was visualized microscopically using HDI-albumin conjugates prepared with fluorescently labelled albumin. In vivo, human HDI exposure was performed via a specific inhalation challenge, and subsequent changes in PBMCs and serum proteins were measured by flow cytometry and ELISA. Genotypes were determined by PCR. RESULTS: Human monocytes take up HDI-albumin conjugates and undergo marked changes in morphology and gene/protein expression in vitro. The most significant (P-values 0.007-0.05) changes in microarray gene expression were noted in lysosomal genes, especially peptidases and proton pumps involved in antigen processing. Chemokines that regulate monocyte/macrophage trafficking (MIF, MCP-1) and pattern-recognition receptors that bind chitin (chitinases) and oxidized low-density lipoprotein (CD68) were also increased following isocyanate-albumin exposure. In vivo, HDI-exposed subjects exhibited a drastic increase in the percentage of PBMCs with the same HDI-albumin responsive phenotype characterized in vitro (HLA-DR(+)/CD11c(+) with altered light scatter properties). An exposure-dependent decrease (46+/-11%; P<0.015) in serum concentrations of chitinase 3-like-1 was also observed in individuals who lack the major (type 1) human chitinase (due to genetic polymorphism), but not in individuals possessing at least one functional chitinase-1 allele. CONCLUSIONS: Previously unrecognized innate immune responses to HDI and HDI-albumin conjugates could influence the clinical spectrum of exposure reactions. [Description provided by NIOSH]
• Subjects:
  Air Pollutants, Occupational Hypersensitivity Isocyanates Occupational Diseases Occupational Exposure Occupational Health Particulate Matter Respiratory Tract Diseases Safety Solvents Workplace

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• Keywords:
  Airborne-fibers Airborne-particles Allergic-disorders Allergic-reactions Mathematical-models Models Occupational-diseases Occupational-exposure Particle-aerodynamics Particulate-dust Particulate-sampling-methods Pulmonary-system-disorders Quantitative-analysis Vapors Work-environment Work-practices

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• ISSN:
  0954-7894
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  California ; Connecticut ; Kentucky ; Massachusetts ; OSHA Region 1 ; OSHA Region 4 ; OSHA Region 9
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  38
• Issue:
  6
• NIOSHTIC Number:
  nn:20034227
• Citation:
  Clin Exp Allergy 2008 Jun; 38(6):957-967
• Contact Point Address:
  Adam V. Wisnewski, Department of Internal Medicine, Yale School of Medicine, 1 Gilbert Street, TAC-S415, New Haven, CT 06520
• Email:
  adam.wisnewski@yale.edu
• Federal Fiscal Year:
  2008
• NORA Priority Area:
  Disease and Injury: Asthma and Chronic Obstructive Pulmonary Disease
• Performing Organization:
  Yale University, New Haven, Connecticut
• Peer Reviewed:
  True
• Start Date:
  19970901
• Source Full Name:
  Clinical and Experimental Allergy
• End Date:
  20020831
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:6ac1e143e6a2d45fc93a4518a4a1808c9e941098ec6025407d2576769c05bac472f0ed809ef3e6c6645bb83ce2ebab081f503c991bfc69542bd62601477795db
• Download URL:
  https://stacks.cdc.gov/view/cdc/189528/cdc_189528_DS1.pdf
• File Type:
  [PDF - 1.57 MB ]