Graphene oxide attenuates Th2-type immune responses, but augments airway remodeling and hyperresponsiveness in a murine model of asthma.
Several lines of evidence indicate that exposure to nanoparticles (NPs) is able to modify airway immune responses, thus facilitating the development of respiratory diseases. Graphene oxide (GO) is a promising carbonaceous nanomaterial with unique physicochemical properties, envisioned for a multitude of medical and industrial applications. In this paper, we determined how exposure to GO modulates the allergic pulmonary response. Using a murine model of ovalbumin (OVA)-induced asthma, we revealed that GO, given at the sensitization stage, augmented airway hyperresponsiveness and airway remodeling in the form of goblet cell hyperplasia and smooth muscle hypertrophy. At the same time, the levels of the cytokines IL-4, IL-5, and IL-13 were reduced in broncho-alveolar lavage (BAL) fluid in GO-exposed mice. Exposure to GO during sensitization with OVA decreased eosinophil accumulation and increased recruitment of macrophages in BAL fluid. In line with the cytokine profiles, sensitization with OVA in the presence of GO stimulated the production of OVA-specific IgG2a and down-regulated the levels of IgE and IgG1. Moreover, exposure to GO increased the macrophage production of the mammalian chitinases, CHI3L1 and AMCase, whose expression is associated with asthma. Finally, molecular modeling has suggested that GO may directly interact with chitinase, affecting AMCase activity, which has been directly proven in our studies. Thus, these data show that GO exposure attenuates Th2 immune response in a model of OVA-induced asthma, but leads to potentiation of airway remodeling and hyperresponsiveness, with the induction of mammalian chitinases.
Department of Pathology, University of Pittsburgh School of Medicine , Pittsburgh, Pennsylvania 15260, United States.
Michael R
MR
Shurin
Naveena
N
Yanamala
Elena R
ER
Kisin
Alexey V
AV
Tkach
Galina V
GV
Shurin
Ashley R
AR
Murray
Howard D
HD
Leonard
Jeffrey S
JS
Reynolds
Dmirtiy W
DW
Gutkin
Alexander
A
Star
Bengt
B
Fadeel
Kai
K
Savolainen
Valerian E
VE
Kagan
Anna A
AA
Shvedova
D056151:Airway Remodeling / Q000187:drug effects*; D000818:Animals; D001665:Binding Sites; D001992:Bronchoalveolar Lavage Fluid; D002688:Chitinases / Q000378:metabolism; D004195:Disease Models, Animal; D006108:Graphite / Q000737:chemistry*; D007107:Immune System; D007073:Immunoglobulin E / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D007249:Inflammation; D018793:Interleukin-13 / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D015848:Interleukin-5 / Q000276:immunology; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D036103:Nanotechnology / Q000379:methods*; D010087:Oxides / Q000737:chemistry*; D018418:Th2 Cells / Q000276:immunology*
D007074:Immunoglobulin G; D018793:Interleukin-13; D015848:Interleukin-5; D010087:Oxides; D015847:Interleukin-4; D007073:Immunoglobulin E; D006108:Graphite; D002688:Chitinases