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Published on: August 26, 2016
Phagocytic cells internalize ZnO particles by FcγII/III-receptor pathway
Ruchi Roy1, L K S Chauhan2, Mukul Das1
1Food, Drug and Chemical Toxicology Group, Indian Institute of Toxicology Research, M.G. Marg. Post Box No. 80, Lucknow 226001, India; Academy of Scientific and Innovative Research (AcSIR), New Delhi, India.
Abstract:
The present study investigates the process of internalization for bulk ZnO particles in macrophages, and further elucidates the underlying mechanism. Since macrophages are active phagocytes and phagocytosis is a size dependent phenomenon, therefore we hypothesized that bulk ZnO may internalize into macrophages by phagocytic pathways. Interestingly, the phagocytic activity got enhanced in bulk ZnO treated macrophages. Moreover, the bulk ZnO treated macrophages internalized via FcγR-II/III, complement and scavenger-receptor pathways. To confirm the specificity of phagocytic pathway, the uptake was also analyzed in splenocytes where phagocytic (monocytes) and non-phagocytic cells (lymphocytes) are present. It was observed that no significant uptake of bulk ZnO in case of lymphocytes whereas significant uptake in monocytes. Henceforth, our quest for uptake mechanisms also revealed that severe plasma membrane extensions (pseudopodia), FcγR clustering over the surface of macrophages and activation of FcγR signaling were the key players for bulk ZnO uptake; whereas clathrin or caveolae mediated endocytic pathways contributed less. Uptake of these particles was further strengthened by the ZnO-induced activation of the Src-kinase p-Lyn, phospho-tyrosine kinases Syk (spleen tyrosine kinase), p-PLC-γ and PI3K (phosphatidylinositol 3-kinase). Our findings illustrate that the phagocytic nature of macrophages could have led to higher uptake of bulk ZnO.
Insights
Bulk zinc oxide (ZnO) particles are internalized by macrophages primarily through phagocytosis, a process enhanced by ZnO exposure. This uptake involves specific receptor pathways and cellular machinery, highlighting ZnO
Area of Science:
- Cell Biology
- Immunology
- Nanotoxicology
Background:
- Macrophages are key immune cells involved in clearing foreign particles.
- Phagocytosis, a primary cellular uptake mechanism, is known to be size-dependent.
- Understanding nanoparticle internalization is crucial for assessing potential biological effects.
Purpose of the Study:
- To investigate the internalization process of bulk zinc oxide (ZnO) particles in macrophages.
- To elucidate the specific cellular pathways involved in ZnO uptake.
- To determine the role of macrophage phagocytic activity in ZnO internalization.
Main Methods:
- Treatment of macrophages with bulk ZnO particles.
- Analysis of ZnO uptake in splenocytes (containing monocytes and lymphocytes).
- Investigation of cellular signaling pathways (FcγR, Src-kinase, PI3K) and endocytic routes (clathrin, caveolae).
Main Results:
- Bulk ZnO particles were significantly internalized by macrophages, with enhanced phagocytic activity observed.
- Uptake occurred via FcγR-II/III, complement, and scavenger-receptor pathways.
- ZnO uptake was specific to phagocytic monocytes, with minimal internalization in lymphocytes.
- Key mechanisms included pseudopodia formation, FcγR clustering, and activation of Src-kinase, Syk, PLC-γ, and PI3K signaling pathways.
Conclusions:
- Macrophage phagocytosis is the predominant pathway for bulk ZnO particle internalization.
- ZnO uptake is mediated by specific immune receptor pathways and intracellular signaling.
- The findings provide insights into the interaction of ZnO particles with immune cells.
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