Carbon Nanotube Immunotoxicity in Alveolar Epithelial Type II Cells Is Mediated by Physical Contact-Independent Cell-Cell Interaction with Macrophages as Demonstrated in an Optimized Air-Liquid Interface (ALI) Coculture Model.
Nanomaterials (Basel)
; 14(15)2024 Jul 29.
Article
en En
| MEDLINE
| ID: mdl-39120378
ABSTRACT
There is a need for the assessment of respiratory hazard potential and mode of action of carbon nanotubes (CNTs) before their approval for technological or medical applications. In CNT-exposed lungs, both alveolar macrophages (MФs), which phagocytose CNTs, and alveolar epithelial type II cells (AECII cells), which show tissue injury, are impacted but cell-cell interactions between them and the impacted mechanisms are unclear. To investigate this, we first optimized an air-liquid interface (ALI) transwell coculture of human AECII cell line A549 (upper chamber) and human monocyte cell line THP-1 derived macrophages (lower chamber) in a 12-well culture by exposing macrophages to CNTs at varying doses (5-60 ng/well) for 12-48 h and measuring the epithelial response markers for cell differentiation/maturation (proSP-C), proliferation (Ki-67), and inflammation (IL-1ß). In optimal ALI epithelial-macrophage coculture (31 ratio), expression of Ki-67 in AECII cells showed dose dependence, peaking at 15 ng/well CNT dose; the Ki-67 and IL-1ß responses were detectable within 12 h, peaking at 24-36 h in a time-course. Using the optimized ALI transwell coculture set up with and without macrophages, we demonstrated that direct interaction between CNTs and MФs, but not a physical cell-cell contact between MФ and AECII cells, was essential for inducing immunotoxicity (proliferative and inflammatory responses) in the AECII cells.
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Colección:
01-internacional
Base de datos:
MEDLINE
Idioma:
En
Revista:
Nanomaterials (Basel)
Año:
2024
Tipo del documento:
Article
País de afiliación:
Estados Unidos