Loss of Proliferation and Antigen Presentation Activity following Internalization of Polydispersed Carbon Nanotubes by Primary Lung Epithelial Cells

Abstract

Interactions between poly-dispersed acid functionalized single walled carbon nanotubes (AF-SWCNTs) and primary lung epithelial (PLE) cells were studied. Peritoneal macrophages (PMs, known phagocytic cells) were used as positive controls in this study. Recovery of live cells from cultures of PLE cells and PMs was significantly reduced in the presence of AF-SWCNTs, in a time and dose dependent manner. Both PLE cells as well as PMs could take up fluorescence tagged AF-SWCNTs in a time dependent manner and this uptake was significantly blocked by cytochalasin D, an agent that blocks the activity of acto-myosin fibers and therefore the phagocytic activity of cells. Confocal microscopic studies confirmed that AF-SWCNTs were internalized by both PLE cells and PMs. Intra-trachially instilled AF-SWCNTs could also be taken up by lung epithelial cells as well as alveolar macrophages. Freshly isolated PLE cells had significant cell division activity and cell cycling studies indicated that treatment with AF-SWCNTs resulted in a marked reduction in S-phase of the cell cycle. In a previously standardized system to study BCG antigen presentation by PLE cells and PMs to sensitized T helper cells, AF-SWCNTs could significantly lower the antigen presentation ability of both cell types. These results show that mouse primary lung epithelial cells can efficiently internalize AF-SWCNTs and the uptake of nanotubes interfered with biological functions of PLE cells including their ability to present BCG antigens to sensitized T helper cells.

Lipid antigen presentation through CD1d pathway in mouse lung epithelial cells, macrophages and dendritic cells and its suppression by poly-dispersed single-walled carbon nanotubes

“…In a recent study, we have demonstrated that mouse lung epithelial cells may present mycobacterial antigens to sensitized T helper cells through Class II MHC presentation pathway and this presentation is significantly suppressed by AF-SWCNTs (Kumari and Saxena, 2011;Kumari et al, 2012). In the present study, we have extended the research to examine if CD1d lipid presentation takes place in LA-4 lung epithelial cells and to assess the effect if any, of AF-SWCNTs on this process.…”

Poly-dispersed-acid-functionalized-single-walled carbon nanotubes (AF-SWCNTs) are potent inhibitor of BCG induced inflammatory response in macrophage cell lines

“…5a and 5b demonstrate a substantial increase in activity of COX-2 on treatment with autoclaved BCG, which was significantly abrogated on treatment with AF-SWCNTs; the decline being 21% (p<0.05) and 85% (p<0.05) in RAW 264.7 and MH-S cells respectively. Our previous work on AF-SWCNTs has shown that it suppresses B, T and NK cell function and processing and presentation of antigens by macrophages as well as lung epithelial cells [14,12,13,16,15,10]. These studies therefore may suggest that AF-SWCNTs may be a good candidate as a general immunosuppressive agents and perhaps as anti-inflammatory agents.…”

“…Our group has been studying the interactions of AF-SWCNTs with several biological systems, and have demonstrated modulatory effects of AF-SWCNTs on activation and functioning of T cells [12,13], B cells [13,14], antigen presenting cells [15,16], hematopoietic activity in bone marrow [7, 17] and lung epithelial cells [18,15,16]. Since AF-SWCNTs have suppressive effect on many components of the immune system, we hypothesized that AF-SWCNTs may also have a generalized anti-inflammatory effect.…”

Poly dispersed acid-functionalized single walled carbon nanotubes target activated T and B cells to suppress GVHD in mouse model

“…Acid functionalization of single-walled CNTs significantly reduces their in vivo toxicity (Schipper et al, 2008) and enhances their interaction with immune cells , Gazia and El-Magd, 2019. Previous studies have shown that the acid functionalized SWCNTs (AF-4 SWCNTs) modulate erythropoiesis (Bhardwaj and Saxena, 2015, Md and Saxena, 2018, Sachar and Saxena, 2011, downregulate protein and lipid antigen presentation (Rizvi et al, 2015, Kumari et al, 2012, alters epithelial tight junctions (Singh et al, 2020), reduce dendritic cells polarization capacity (Aldinucci et al, 2013), suppress activation of NK cells (Alam et al, 2016) and generation of alloimmune cytotoxic T cells (Alam et al, 2013, Dutt and.…”