title: Phagocytic cells internalize ZnO particles by FcγII/III-receptor pathway.
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.
authors.affiliation: Food, 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.
authors.forename: Ruchi
authors.initials: R
authors.lastname: Roy
authors.affiliation: Electron Microscopy Facility, Indian Institute of Toxicology Research, M.G. Marg. Post Box No. 80, Lucknow 226001, India.
authors.forename: L K S
authors.initials: LK
authors.lastname: Chauhan
authors.affiliation: Food, 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.
authors.forename: Mukul
authors.initials: M
authors.lastname: Das
authors.affiliation: Food, Drug and Chemical Toxicology Group, Indian Institute of Toxicology Research, M.G. Marg. Post Box No. 80, Lucknow 226001, India. Electronic address: anurag1706@gmail.com.
authors.forename: Anurag
authors.initials: A
authors.lastname: Tripathi
authors.affiliation: Food, 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. Electronic address: pddwivedi@yahoo.com.
authors.forename: Premendra D
authors.initials: PD
authors.lastname: Dwivedi
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005260:Female; D007074:Immunoglobulin G / Q000276:immunology; D008264:Macrophages / Q000502:physiology*; D008807:Mice, Inbred BALB C; D010587:Phagocytosis; D017452:Receptors, IgG / Q000276:immunology*; D015398:Signal Transduction; D013154:Spleen / Q000166:cytology; D015034:Zinc Oxide / Q000494:pharmacology*
chemical_list: D007074:Immunoglobulin G; D017452:Receptors, IgG; D015034:Zinc Oxide
keywords: Endocytosis; FcγR signaling; Macrophages; Monocytes; Phagocytosis; ZnO particles