Role of the Zinc in Immunity and Inflammation
BiochemPagesJuly 10, 2015ArticlesComments
The role of zinc ions in immunity and inflammation. Image: Bonaventura et al. 2015
Zinc is a trace element constituting 24th most abundant element of the earth’s crust. It is a micronutrient with some of the most important biological roles. Its steady-state balance in our body is necessary because it is involved in different cellular metabolism and it is also a component of some of the important proteins involved in cell structure and function. zinc plays roles in wound healing, cellular respiration (required for the carbonic anhydrase), immune function, protein synthesis, DNA synthesis, cell division, etc.
Zn2+ ions are hydrophilic and, therefore, cannot pass through the cell membrane. They require membrane transporter to get into the cell and out of the cell. There are two families of transporter proteins SLC39 (Zrt-Irt-Protein or ZIPs) and SLC30 (Zn-transporters or ZnTs). There are 14 types of ZIPs that promote Zn2+ ion transport into the cytoplasm or across the membrane vesicles. These transporters have a similar molecular architecture with 8 transmembrane domains and a pore (cavity) through which ions can pass. While there are 10 types of ZnT proteins involved in the transport of the Zn2+ ions out of the cytosol or into the intracellular membrane vesicles.
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Intracellular sequestered membrane vesicle of Zn2+ ions is called as zincosome. Formation of zincosome is mediated by Zn chaperone called as metallothioneins. During zincosome formation, zinc is chelated by metallothioneins into the cytosol and then enclosed into the membrane vesicle. Metallothioneins are the cysteine-rich metal binding proteins involved in regulation of the Zn homeostasis at the cytoplasmic level and also act as a Zn pool. However, metallothionein can also bind to cadmium, copper, magnesium, calcium, and those ions may affect the zinc absorption.
The main functions of the zinc metal ions in the body are of three types structural, catalytic and co-catalytic. The structural role of Zinc is to maintain the structure of the protein in the same way to that of the disulfide bridge. However, removal of the Zinc may not affect the enzyme activity. The catalytic role of the Zn is that it participates directly in the bond forming and bond breaking steps and co-catalytic role can be seen as it affects the catalysis by stabilizing the active site conformation of the enzyme.
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Zn2+ ion also plays roles in signal transduction where it acts as an intracellular signaling molecule. It performs its role in two ways. One is through the neurotransmission where it acts as a neurotransmitter transmitting information through the neurons. It is released into the synaptic cleft from membrane enclosed synaptic vesicles by exocytosis. Thus released Zn2+ ions are then absorbed by neighboring cells through gated Zn channels. In the second way, it acts as an intracellular second messenger. Cytokines or growth factors secret nitric oxide and stimulate the release of Zn2+ ions from metallothioneins.
Zn signaling can either be transcription dependent leading to the late Zinc signaling or transcription independent leading to the early Zn signaling. In late Zn signaling, the intracellular levels of the Zn2+ ions are altered several hours after the extracellular stimulation through the changes in Zn transporter expression while, in early Zn signaling, level of the Zn changes rapidly. But the early Zn signaling and late Zn signaling both are involved in varieties of physiological responses including immune function, cell development, and apoptosis.
Zn2+ ions also play a role in the regulation of the cell proliferation and differentiation where it acts as a structural component of different proteins of the transcriptional machinery such as transcription factors and the ribosome. The presence of Zn is also necessary during the DNA replication and cell cycle.
The role of zinc in the immune system. Image: Bonaventura et al. 2015
It has also been found that Zinc plays a role in immunity where it acts as a chemoattractant for some immune cells. In vitro study reveals that Zinc deficiency leads to the reduced PMN chemo toxicity while the supply of the Zn2+ ions has the inverse effect.
Zinc deficiency decreases phagocytosis while zinc supplement increases the phagocytosis of the immune cells. zinc deficiency causes thymic atrophy and subsequent T cell lymphopenia thus affecting the development and functions of the T cells. However, development and functions of the B cells are less affected by zinc deficiency than that of the T cells.
Acrodermatitis enteropathica is one of the most important diseases caused by the zinc deficiency. It is a rare genetic disorder caused due to the mutation in the gene encoding ZIP4 responsible for the zinc uptake. The symptoms if this disease includes hyperpigmented skin lesions, defective growth, thymic atrophy, lymphopenia, etc.