Eosinophilia and Leucocytic DNA damage

1. Introduction

Inflammation is a fundamental immune response. Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are produced in response to pathogens, but they can also cause DNA damage (Kay et al., 2019). The major immune cells involved in ROS production include neutrophils, macrophages, and eosinophils. Eosinophils have been found to exhibit a greater superoxide generation rate and longer latency period than neutrophils (Petreccia et al., 1987), while eosinophilia may indicate a chronic health condition (Valent et al., 2021).

Eosinophilia refers to an abnormal increase in eosinophils in peripheral blood. These cells possess bactericidal, anti-parasitic, and cell-killing functions, primarily targeting microbial parasite infections and participating in inflammatory responses (Lombardi et al., 2022). Activation of eosinophils by immunoglobulins, cytokines, and other lipid mediators triggers a cascade of inflammatory reactions in the body, leading to tissue damage (Ramirez et al., 2018). The oxidizing intermediates resulting from eosinophil-mediated inflammation significantly contribute to increased oxidative stress and DNA damage (Henderson et al., 2001). Basic proteins and cationic proteins released from eosinophil granules exert toxicity on mammalian cells (Muniz et al., 2012). Eosinophil peroxidase can generate free radicals in the presence of hydrogen peroxide (van Dalen et al., 2006). Animal studies demonstrate that allergens induce the formation of reactive oxygen species in human cell culture models (Chan et al., 2017). In developed countries, helminthic infestations are not major health concerns, but an increase in eosinophil counts is likely due to allergic reactions. Allergy represents an undesirable inflammatory response, and oxidants are released during this process, contributing to oxidative stress in the body. Eosinophils have also been reported to contribute to oxidative stress in uncontrolled asthma (de Groot et al., 2019), while children with allergic rhinitis are found to have higher plasma total oxidant status (Emin et al., 2012).

In the presence of chronic oxidative stress due to eosinophilia, the oxidative stress may contribute damage to peripheral cellular DNA. The aim of the current study was to investigate the association between eosinophils count and detectable leucocytic DNA damage if any.

2. Methods

3. Results

Results showed that eosinophilia subjects demonstrated a higher leucocytic DNA damage than normal group. Comet scores were 92.8 (124.0) in normal subjects while 161.8 (151.1) in eosinophilia group [Mean (SD)] (Figure 1). These findings support our initial hypothesis that DNA damage is elevated during inflammatory states. Additionally, weak positive associations between comet score and eosinophil percentage (r=0.3190, p=0.0010), comet score and eosinophil count (r=0.2608, p=0.0075) were observed. There were no statistically significant differences in age and WBC count between normal and test groups (p>0.05) (Table 1) (Szeto, 2024).

Figure 1. Comet score of normal subjects (n = 52); eosinophilia subjects (n = 52).

Statistically significant difference was seen between eosinophilia and normal subjects. Unpaired t-test (p<0.0124).

4. Discussion

Eosinophil can degranulate and release cytotoxic content at the site of injury which in turn worsens inflammation and tissue damage (Rosenberg et al., 2013). Eosinophil peroxidase in eosinophils can generate potent oxidants to defend the invasion of parasite and likely cause eosinophil-mediated tissue damage (Henderson et al., 2001). It has been reported that blood eosinophil count is associated with eosinophil infiltration in the nasal polyps (El-Anwar et al., 2022) and in colorectal mucosal (Haasnoot et al., 2023). Researchers have also demonstrated the positive correlation between peripheral blood eosinophil count and disease severity in bullous pemphigoid (BP) (Gore Karaali et al., 2021).

Allergens, such as house dust mites, are known to induce DNA damage in bronchial epithelium (Chan et al., 2016). Although the mechanism remains unknown, plasma total antioxidant status is lower in children with asthma bronchiale (Zeyrek et al., 2009). The current results imply that eosinophils might not only be associated with tissue damage but also contribute to DNA damage in peripheral white blood cells. However, there is no evidence to conclude a causal relationship between eosinophil count and leucocytic DNA damage. Pretreatment with antioxidants in mice with induced airway inflammation has been found to lower oxidative stress (Park et al., 2009). Eosinophils in mild asthma have been suggested to contribute to oxidative stress, and treatment of oxidative stress could potentially relieve asthma in humans (de Groot et al., 2019) or serve as beneficial adjunctive therapy (Bowler & Crapo, 2002). This highlights the potential application of peripheral blood cell DNA damage assessment to evaluate the effectiveness of oxidative stress treatment.

Ethics and consent

This study was conducted in accordance with the principles of the Declaration of Helsinki, and all patients provided written informed consent prior to enrollment. Blood samples were from specimens for other laboratory tests and no additional blood sample was taken. The approval was obtained from the Research Ethics Committee. [Protocol No: 2022A]. Permission was obtained from the chairperson of Research Ethics Committee, Macao Society for the Study of Women’s Health on 3rd Jan 2022. Reference number 202201.