Siglecs Modulate Activities of Immune Cells Through Positive and Negative Regulation of ROS Generation

Abstract

Reactive oxygen species (ROS) are a group of oxygen-containing highly-reactive molecules produced from oxidative metabolic processes or in response to intracellular signals like cytokines and external stimuli like pathogen attack. They regulate a range of physiological processes and are involved in innate immune responses against infectious agents. Deregulation of ROS contributes to a plethora of disease conditions. Sialic acids are carbohydrates, present on cell surfaces or soluble proteins. Sialic acid-binding immunoglobulin-like lectins (Siglecs) recognize and bind to sialic acids. These are widely expressed on various types of immune cells. Siglecs modulate immune activation and can promote or inhibit ROS generation under different contexts. Siglecs promote ROS-dependent cell death in neutrophils and eosinophils while limiting oxidative stress associated with chronic obstructive pulmonary disease (COPD), sickle cell disease (SCD), coronavirus disease-2019 (COVID-19), etc. This review distinguishes itself in summarizing the current understanding of the role of Siglecs in moderating ROS production and their distinct effect on different immune cells; that ultimately determine the cellular response and the disease outcome. This is an important field of investigation having scope for both expansion and medical importance.

Melatonin reduces IL‐33 and TSLP expression in human nasal epithelial cells by scavenging ROS directly

“… 18 Low doses of ROS have positive biological effects in maintaining metabolism, signal transduction, cell proliferation, apoptosis, and the aging process. 19 In contrast, excess ROS can have devastating effects on cells, damaging proteins, lipids, and nucleic acids, causing apoptosis and necrosis in more severe cases. 20 Normally, cells can scavenge ROS, such as Nrf2, which is the most important.…”

“…They include superoxide anions (˙O 2− ), hydrogen peroxide (H 2 O 2 ), hydroxyl radicals (˙OH), singlet oxygen (1O 2 ), peroxy radicals (LOO˙), hydrogen peroxide lipids (LOOH), and peroxynitrite (ONOO − ) among others 18 . Low doses of ROS have positive biological effects in maintaining metabolism, signal transduction, cell proliferation, apoptosis, and the aging process 19 . In contrast, excess ROS can have devastating effects on cells, damaging proteins, lipids, and nucleic acids, causing apoptosis and necrosis in more severe cases 20 .…”

Eosinophils from A to Z

“…340 Moreover, crosslinking of siglec-F on mouse eosinophils induced caspase-dependent cell death without ROS production. 340 Ultimately, it was shown that ROS production is essential in the process of EET formation. 146…”

“…341,342 Furthermore, cross-linking of siglec-8 was reported to induce intracellular ROS production, as well as caspase cleavage and a decrease in mitochondrial membrane potential, resulting in apoptosis in resting human eosinophils. 340 Interestingly, siglec-8 cross-linking on IL-5-primed eosinophils has been shown to induce ROS production along with increased phosphorylation of MEK1 and ERK1/2, leading to caspase-independent necrotic death, while the cross-linking of siglec-8 on IL-33-primed eosinophils resulted in enhanced cell death without ROS production. 340 Moreover, crosslinking of siglec-F on mouse eosinophils induced caspase-dependent cell death without ROS production.…”

“…340 Interestingly, siglec-8 cross-linking on IL-5-primed eosinophils has been shown to induce ROS production along with increased phosphorylation of MEK1 and ERK1/2, leading to caspase-independent necrotic death, while the cross-linking of siglec-8 on IL-33-primed eosinophils resulted in enhanced cell death without ROS production. 340 Moreover, crosslinking of siglec-F on mouse eosinophils induced caspase-dependent cell death without ROS production. 340 Ultimately, it was shown that ROS production is essential in the process of EET formation.…”