Single-Walled and Multi-Walled Carbon Nanotubes Promote Allergic Immune Responses in Mice

Abstract

The adjuvant effect of particles on allergic immune responses has been shown to increase with decreasing particle size and increasing particle surface area. Like ultrafine particles, carbon nanotubes (CNTs) have nano-sized dimensions and a large relative surface area and might thus increase allergic responses. Therefore, we examined whether single-walled (sw) and multi-walled (mw) CNTs have the capacity to promote allergic responses in mice, first in an sc injection model and thereafter in an intranasal model. Balb/cA mice were exposed to three doses of swCNT, mwCNT, as well as ultrafine carbon black particles (ufCBPs, Printex90) during sensitization with the allergen ovalbumin (OVA). Five days after an OVA booster, OVA-specific IgE, IgG1, and IgG2a antibodies in serum and the numbers of inflammatory cells and cytokine levels in bronchoalveolar lavage fluid (BALF) were determined. Furthermore, ex vivo OVA-induced cytokine release from mediastinal lymph node (MLN) cells was measured. In separate experiments, differential cell counts were determined in BALF 24 h after a single intranasal exposure to the particles in the absence of allergen. We demonstrate that both swCNT and mwCNT together with OVA strongly increased serum levels of OVA-specific IgE, the number of eosinophils in BALF, and the secretion of Th2-associated cytokines in the MLN. On the other hand, only mwCNT and ufCBP with OVA increased IgG2a levels, neutrophil cell numbers, and tumor necrosis factor-alpha and monocyte chemoattractant protein-1 levels in BALF, as well as the acute influx of neutrophils after exposure to the particles alone. This study demonstrates that CNTs promote allergic responses in mice.

In vitro and in vivo toxicity assessment of nanoparticles

“…The study recognized the SW-CNTs as a respiratory toxicant, responsible for neurotoxicity and cell cycle defects. MW-CNTs are also known for increased micronuclei frequency and chromosomal aberrations, promotion of allergic response in mice, activation of cyclooxygenase enzymes through suppression of systemic immune function in spleen and altered gene expression in the liver [173][174][175][176][177]. Other effects of MW-CNTs include apoptosis, phenotypic defects, toxicity in bacteria and formation of abnormal spinal cords in zebrafish embryo [178][179][180].…”

Assessing nanoparticle toxicity in cell-based assays: influence of cell culture parameters and optimized models for bridging the in vitro–in vivo gap

“…The protein corona can also stimulate opsonisation by macrophages in vivo, thereby activating the complement system and evoking an immune reaction 70 . Another plausible pathway to immunotoxicity is the enhancement of an allergic immune response, which by Nygaard et al observed for single-and multi-walled carbonnotubes (CNT) in mice 71,72 .…”

Carbon nanotube interaction with extracellular matrix proteins producing scaffolds for tissue engineering

“…44 Then the entire process of reconstitution occurs, from the successful interaction between cells and cells and ECM, avoiding initiation of an immune response. 45 One of the most popular materials used in scaffolds for tissue engineering was discovered in 1991 and revolutionized the research field: CNTs. 17 These nanotubes, since they started being studied, have demonstrated a huge number of interesting characteristics; for example, they have remarkable electrical and mechanical properties and chemical stability.…”

“…50 Nygaard and collaborators demonstrated that in mice, the adjuvant effect of particles on allergic immune responses increases with decreasing particle size and increasing particle surface area, and that CNTs promote allergic responses in mice. 45 In this way, researchers face the challenge of modifying CNT surface to avoid evoking immune responses and to promote successful regeneration as part of a scaffold.…”