The capacity of particles to increase allergic sensitization is predicted by particle number and surface area, not by particle mass

Toxicol Sci. 2004 Dec;82(2):515-24. doi: 10.1093/toxsci/kfh287. Epub 2004 Sep 29.

Abstract

Particle exposure has traditionally been monitored as mass concentration of PM10 (particles with an aerodynamic diameter less than 10 microm), more recently also as PM2.5. The mass concentration is strongly influenced by the large particles. Therefore, particle mass is a poor measure for characterizing the amount of the small, possibly more biologically potent particles. We used polystyrene particles (PSP) ranging in diameter from 0.0588 to 11.14 microm, carbon black (CB), and diesel exhaust particles (DEP), to study the adjuvant effect of particles on the immune response to the allergen ovalbumin (OVA) after sc injection into the footpad of BALB/cA mice. At a given mass dose, the small particles (0.0588 and 0.202 microm PSP, CB, and DEP) increased the allergen-specific IgE serum levels to a substantially higher degree than the larger particles (1.053, 4.64, and 11.14 microm PSP). Further, in the draining lymph node during the primary response, the fine particles (0.202 microm) with OVA increased cell numbers, expression of surface markers (CD19, MHC class II, CD86, and CD23) and ex vivo production of IL-4 and IL-10, whereas the largest (11.14 microm) particles did not. Linear regression analyses indicated that the IgE response was not predicted by particle mass (R2 = 0.06), but was predicted by the total particle surface area (R2 = 0.64), number of particles (R2 = 0.62), and particle diameter (R2 = 0.58). In conclusion, we found that fine particles exerted stronger adjuvant effects on allergic responses than larger particles at equal mass doses. Consequently, the dose described as total particle surface area or particle number predicts the adjuvant effect of particles better than the currently used particle mass.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic
  • Animals
  • Antigens, Surface / analysis
  • Carbon / toxicity
  • Cytokines / analysis
  • Cytokines / metabolism
  • Dose-Response Relationship, Drug
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Hypersensitivity / pathology*
  • Immunoglobulin E / biosynthesis
  • Immunoglobulin G / biosynthesis
  • Lymph Nodes / immunology
  • Lymph Nodes / pathology
  • Lymphocyte Count
  • Lymphocytes / immunology
  • Mice
  • Mice, Inbred BALB C
  • Ovalbumin / immunology
  • Particle Size
  • Phenotype
  • Polystyrenes / toxicity
  • Predictive Value of Tests
  • Regression Analysis
  • Surface Properties
  • Thymidine / metabolism
  • Vehicle Emissions / toxicity

Substances

  • Adjuvants, Immunologic
  • Antigens, Surface
  • Cytokines
  • Immunoglobulin G
  • Polystyrenes
  • Vehicle Emissions
  • Immunoglobulin E
  • Carbon
  • Ovalbumin
  • Thymidine