Fibrous nanocellulose, crystalline nanocellulose, carbon nanotubes, and crocidolite asbestos elicit disparate immune responses upon pharyngeal aspiration in mice

Abstract

With the rapid development of synthetic alternatives to mineral fibers, their possible effects on the environment and human health have become recognized as important issues worldwide. This study investigated effects of four fibrous materials, i.e. nanofibrillar/nanocrystalline celluloses (NCF and CNC), single-walled carbon nanotubes (CNTs), and crocidolite asbestos (ASB), on pulmonary inflammation and immune responses found in the lungs, as well as the effects on spleen and peripheral blood immune cell subsets. BALB/c mice were given NCF, CNC, CNT, and ASB on Day 1 by oropharyngeal aspiration. At 14 days post-exposure, the animals were evaluated. Total cell number, mononuclear phagocytes, polymorphonuclear leukocytes, lymphocytes, and LDH levels were significantly increased in ASB and CNT-exposed mice. Expression of cytokines and chemokines in bronchoalveolar lavage (BAL) was quite different in mice exposed to four particle types, as well as expression of antigen presentation-related surface proteins on BAL cells. The results revealed that pulmonary exposure to fibrous materials led to discrete local immune cell polarization patterns with a T2-like response caused by ASB and T1-like immune reaction to NCF, while CNT and CNC caused non-classical or non-uniform responses. These alterations in immune response following pulmonary exposure should be taken into account when testing the applicability of new nanosized materials with fibrous morphology.

The Crystallinity and Aspect Ratio of Cellulose Nanomaterials Determine Their Pro‐Inflammatory and Immune Adjuvant Effects In Vitro and In Vivo

“…While currently there are no published data revealing a safety concern for nanocellulose in the workplace or in consumer products, experimental evidence has been collected for the potential hazardous effects of CNCs and CNFs . While most cellular studies have addressed cytotoxicity, inflammation and genotoxicity, which can be related to differences in the cellular uptake of CNCs versus CNFs or their ability to generate oxidative stress, most in vivo studies have focused on the effects in the lung and the reproductive system . For instance, pulmonary exposure to CNCs is capable of generating dose‐dependent pro‐inflammatory effects and oxidative stress, while CNFs are capable of inducing TH1 polarizing effects in the lung .…”

“…While most cellular studies have addressed cytotoxicity, inflammation and genotoxicity, which can be related to differences in the cellular uptake of CNCs versus CNFs or their ability to generate oxidative stress, most in vivo studies have focused on the effects in the lung and the reproductive system . For instance, pulmonary exposure to CNCs is capable of generating dose‐dependent pro‐inflammatory effects and oxidative stress, while CNFs are capable of inducing TH1 polarizing effects in the lung . Moreover, pulmonary CNC exposure can exert systemic effects, e.g., influencing sperm counts, mobility, and DNA strand breaks in the male reproductive system .…”

“…These series of intracellular events can lead to pro‐inflammatory and immunogenic effects in the innate immune system. While it has been shown that nanocellulose can exert TH1 immune polarizing effects in the lung, no detailed attempt has been made to elucidate the structure–activity relationships that underpin these immune effects . In order to assess the effect of fiber length, crystallinity, and surface reactivity of CNFs and CNCs in the innate immune system, we acquired a panel of nine nanocellulose materials in which the characterization of these properties were used for understanding of their structure–activity relationships in macrophages and dendritic cells.…”

Salubrious effects of a vermiculite–cellulose‐based bionanocomposite on oxidative stress indices and histomorphology of male Wistar rats

“…The adverse effects on spermatogenesis and caudal epididymal sperm in mice administered with CNC for 3 weeks have been documented (Farcas et al, ). Similarly, Park et al () showed that CNC elicited alterations in immune response following pulmonary exposure to BALB/c mice. The toxicity of sulphonated nanocellulose in renal tissue of rats has also been reported (Adewuyi, Otuechere, Adebayo, Anazodo, & Pereira, ).…”

Nanocellulose in Biotechnology and Medicine: Focus on Skin Tissue Engineering and Wound Healing

“…Pulmonary exposure to NFC led to discrete local immune cell polarization patterns with TH1-like immune reaction, while CNC caused non-classical or non-uniform responses. However, the response to both types of nanocellulose was milder than the response to asbestos and carbon nanotubes [276]. In addition, curcumin was able to suppress, at least in part, the immune response to cationic needle-like cellulose nanocrystals, as observed by diminished IL-1β secretion in mouse J774A.1 macrophages primed with LPS [19].…”