Journal of Clinical Immunology

, Volume 28, Issue 5, pp 571–580 | Cite as

Histamine Release and Inflammatory Cell Infiltration in Airway Mucosa in Methylene Diphenyl Diisocyanate (MDI)-Induced Occupational Asthma

  • Gyu-Young Hur
  • Seung-Soo Sheen
  • Young-Mi Kang
  • Dong-Hee Koh
  • Han-Jung Park
  • Young-Min Ye
  • Hyun-ee Yim
  • Kyoo-Sang Kim
  • Hae-Sim Park



Although methylene diphenyl diisocyanate (MDI) is widely used in industries, there have been few studies of the pathogenic mechanisms of MDI-induced occupational asthma (MDI-OA).


We performed immunohistochemical analyses, measured inflammatory mediators and cytokines, and quantified histamine release (HR) from peripheral basophils in MDI-OA patients. Thirteen MDI-exposed workers (five MDI-OA, two MDI-induced esoinophilic bronchitis, and six asymptomatic exposed controls, AEC) were enrolled.

Results and Discussion

Immunochemical analyses indicated significantly increased anti-eosinophilic cationic protein-stained cells in MDI-OA patients as compared with controls (P < 0.05). Sputum eosinophil cationic protein levels were increased after MDI-specific inhalation challenge test in MDI-OA/EB patients (P < 0.02). Sputum eosinophil counts were highly correlated with IL-8 and MMP-9 levels (P < 0.05 and P < 0.01, respectively). Basophil HR was significantly increased in MDI-OA patients after stimulations with anti-IgG4 and MDI–human serum albumin conjugates (both P < 0.05). Eosinophil activation is a major feature of airway inflammation in MDI-OA patients. Increased HR by MDI may contribute to the pathogenic mechanisms of MDI-OA.


Eosinophil mast cell MDI occupational asthma 



allergic asthma


asymptomatic exposed controls


eosinophil cationic protein


human serum albumin


histamine release


methylene diphenyl diisocyanate


methylene diphenyl diisocyanate-induced occupational eosinophilic bronchitis


methylene diphenyl diisocyanate-induced occupational asthma


methylene diphenyl diisocyanate-induced occupational asthma or eosinophilic bronchitis


matrix metalloproteinase-9




toluene diisocyanate


toluene diisocyanate-induced occupational asthma


tissue inhibitor of metalloproteinase-1


vascular endothelial growth factor


work-related respiratory symptoms



We would like to thank Dr. Adam Wisnewski of Yale University for providing the MDI–HSA conjugates used in this study. This study was supported by a grant from the Korean Health 21 R&D Project of the Ministry of Health and Welfare, Republic of Korea (A050571).


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Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Gyu-Young Hur
    • 1
  • Seung-Soo Sheen
    • 2
  • Young-Mi Kang
    • 1
  • Dong-Hee Koh
    • 4
  • Han-Jung Park
    • 1
  • Young-Min Ye
    • 1
  • Hyun-ee Yim
    • 3
  • Kyoo-Sang Kim
    • 4
  • Hae-Sim Park
    • 1
  1. 1.Department of Allergy and RheumatologyAjou University School of MedicineYoungtong-guKorea
  2. 2.Department of Pulmonary and Critical Care MedicineAjou University School of MedicineSuwonKorea
  3. 3.Department of PathologyAjou University School of MedicineSuwonKorea
  4. 4.Occupational Safety and Health Research InstituteKorea Occupational Safety and Health AgencyIncheonKorea

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