Title
Coadministration of antigen and particles optimally stimulates the immune response in an intranasal administration model in mice
Author
van Zijverden, M.
de Haar, C.
van Beelen, A.
van Loveren, H.
Penninks, A.
Pieters, R.
Centraal Instituut voor Voedingsonderzoek TNO
Publication year
2001
Abstract
Some particulate matter is known to affect human health, yet the mechanism(s) by which it acts is largely unknown. One of the factors that may play a role in the immune- stimulating activity of particles is binding of allergen to particles. This may turn the particles into allergen carriers, resulting in antigen deposition within the altered inflammatory microenvironment created by the particles. We compared the effectivity of simultaneous versus separate administration of antigen and particles during sensitization in an intranasal exposure model in BALB/c mice. Sensitization consisted of three separate doses (10 μg) of TNP-OVA at Days 1, 2, and 3. Two hundred micrograms of carbon black particles (CBP) were administered either 1 day before sensitization (Day 0), 1 day after sensitization (Day 4), or during sensitization. The latter was performed either at Day 1 (200 μg) or at Days 1, 2, and 3 (67 μg/day). At Day 10 a challenge with 10 μg of TNP-OVA was performed, and at Day 15 the immune response was assessed. The total number of cells as well as antibody-forming cells (AFC) in lymph nodes draining the lung (peribronchial lymph nodes [PBLN]) were determined, and immunoglobulin levels in blood were assessed. Cell numbers of PBLN increased significantly in all particle-treated groups compared to controls. The number of TNP-specific IgG1-forming cells in the groups receiving particles during sensitization was significantly higher than control level. Only groups receiving particles during or before sensitization displayed significantly higher IgG1 levels than controls, in contrast to the group receiving particles after sensitization. Only in animals receiving three doses of 67 μg during sensitization did TNP-specific IgE increase significantly compared to controls. IgG2a did not show significant differences compared to controls, indicating that the response is predominantly Th2 mediated. These data indicate that coadministration of particles at all time points of antigen dosing is the most effective way to stimulate an immune response in our model compared to separate particle and antigen dosing. Also, administration shortly before antigen administration was effective in stimulating an immune response, suggesting that time-dependent processes are involved in immune-stimulating activity of particles, supporting the important role of the altered inflammatory microenvironment created by the particles. © 2001 Elsevier Science. Chemicals/CAS: Carbon, 7440-44-0; Immunoglobulin E, 37341-29-0; Immunoglobulin G; Ovalbumin, 9006-59-1; trinitrophenyl-ovalbumin
Subject
Nutrition
Administration, Intranasal
Animals
Antibody-Producing Cells
Carbon
Cell Count
Disease Models, Animal
Drug Administration Schedule
Enzyme-Linked Immunosorbent Assay
Female
Hypersensitivity
Immunoglobulin E
Immunoglobulin G
Lung
Lymph Nodes
Mice
Mice, Inbred BALB C
Ovalbumin
Particle Size
Time Factors
Animalia
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http://resolver.tudelft.nl/uuid:1497dca3-8811-4556-bdba-38940747673d
DOI
https://doi.org/10.1006/taap.2001.9306
TNO identifier
87738
ISSN
0041-008X
Source
Toxicology and Applied Pharmacology, 177 (3), 174-178
Document type
article