Document Detail

Immunization and challenge with toluene diisocyanate decrease tachykinin and calcitonin gene-related peptide immunoreactivity in guinea pig central airways.
MedLine Citation:
PMID:  9655739     Owner:  NLM     Status:  MEDLINE    
Toluene diisocyanate (TDI) is a potent sensitizer that causes occupational asthma in a significant proportion of subjects exposed. We used an animal model to investigate whether neuropeptide changes occur in the airways of immunized and TDI-challenged guinea pigs. Animals were immunized by weekly intradermal injections, challenged with TDI (5 to 20 ppb) after the third injection, and killed 6 h after exposure. Control guinea pigs received injections of saline. Lung tissue was processed immediately and analyzed for nerves using the streptavidin-biotin complex peroxidase method with antisera to the neural marker protein gene product 9.5 (PGP 9.5), substance P (SP), and calcitonin gene- related peptide (CGRP). We also quantified the inflammatory infiltrate in the submucosa of central airways, and we measured the serum level of specific IgG and IgG1. Specific antibodies against TDI were present only in immunized animals. Immunized as compared with nonimmunized animals had a significant increase in eosinophils in the submucosa of central airways, and a further increase was observed 6 h after TDI challenge. Immunization and TDI challenge did not modify the number of mononuclear cells in the submucosa of central airways in both nonimmunized and immunized animals. TDI exposure did not change the overall innervation in both nonimmunized and immunized animals, but the density of PGP 9.5-positive nerves was significantly different between nonimmunized and immunized TDI-challenged animals. The density of SP-, and CGRP-immunostained nerves was significantly lower in immunized TDI-challenged than in nonimmunized animals. TDI exposure significantly decreased the density of SP-positive nerves in nonimmunized animals. A negative relationship was found between the presence of airway inflammation, as indexed by eosinophil cell infiltration, and the density of PGP 9.5-, SP-, and CGRP-immunostained nerves. In conclusion, TDI produces airway inflammation and neuropeptides changes in the central airways of immunized guinea pigs 6 h after TDI challenge. These findings support an interaction between tachykinins, inflammatory (i.e., eosinophils) and possibly immune cells.
C E Mapp; R E Lucchini; D Miotto; P Chitano; L Jovine; M Saetta; P Maestrelli; D R Springall; J Polak; L M Fabbri
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  American journal of respiratory and critical care medicine     Volume:  158     ISSN:  1073-449X     ISO Abbreviation:  Am. J. Respir. Crit. Care Med.     Publication Date:  1998 Jul 
Date Detail:
Created Date:  1998-07-30     Completed Date:  1998-07-30     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9421642     Medline TA:  Am J Respir Crit Care Med     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  263-9     Citation Subset:  AIM; IM    
Institute of Occupational Medicine, University of Padova, Padova; and Institute of Infectious and Respiratory Diseases, University of Ferrara, Ferrara, Italy.
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MeSH Terms
Bronchial Provocation Tests
Calcitonin Gene-Related Peptide / analysis*
Cell Count
Disease Models, Animal
Eosinophils / pathology
Guinea Pigs
Immunoglobulin G / immunology
Inflammation / pathology
Nerve Fibers / pathology
Respiratory System / immunology,  metabolism,  pathology*
Substance P / analysis*
Tachykinins / analysis
Toluene 2,4-Diisocyanate* / immunology
Reg. No./Substance:
0/Immunoglobulin G; 0/Tachykinins; 33507-63-0/Substance P; 584-84-9/Toluene 2,4-Diisocyanate; 83652-28-2/Calcitonin Gene-Related Peptide

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