title: Coadministration of antigen and particles optimally stimulates the immune response in an intranasal administration model in mice.
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 efficacy 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 microg) 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 microg) or at Days 1, 2, and 3 (67 microg/day). At Day 10 a challenge with 10 microg 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 microg 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.
authors.affiliation: TNO Nutrition and Food Research, Zeist, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: van Zijverden
authors.forename: C
authors.initials: C
authors.lastname: de Haar
authors.forename: A
authors.initials: A
authors.lastname: van Beelen
authors.forename: H
authors.initials: H
authors.lastname: van Loveren
authors.forename: A
authors.initials: A
authors.lastname: Penninks
authors.forename: R
authors.initials: R
authors.lastname: Pieters
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000921:Antibody-Producing Cells / Q000276:immunology / Q000473:pathology; D002244:Carbon / Q000008:administration & dosage* / Q000276:immunology*; D002452:Cell Count; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006967:Hypersensitivity / Q000097:blood / Q000276:immunology* / Q000473:pathology; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D008168:Lung; D008198:Lymph Nodes / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000008:administration & dosage* / Q000276:immunology*; D010316:Particle Size; D013997:Time Factors
chemical_list: D007074:Immunoglobulin G; C038600:trinitrophenyl-ovalbumin; D007073:Immunoglobulin E; D002244:Carbon; D010047:Ovalbumin