Equine neutrophils and their role in ischemia reperfusion injury and lung inflammation

Anderson, Stacy; Singh, Baljit

doi:10.1007/s00441-017-2770-1

Cited by 12 publications

(7 citation statements)

References 84 publications

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“…These works span the spectrum, ranging from human critical care medicine (McDonald 2018) to bovine health and disease (Bassel and Caswell 2018), to the role of neutrophils in equine lung inflammation and ischemia reperfusion injury (Anderson and Singh 2018). These works bring our understanding of the neutrophil full circle, from mapping of specific effector functions and cell recruitment pathways to the role these cells play in the generation, and resolution, of disease.…”

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confidence: 99%

Neutrophils: multitasking first responders of immunity and tissue homeostasis

2018

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From an evolutionary perspective, neutrophils are one of oldest immune cell types and represent a key first responder to infection and tissue injury (Leiding 2017). These early immune components first appear in simple invertebrates, such as cnidarians, as cells called amebocytes. In higher invertebrates, these primordial neutrophils take the form of hemocytes, cells that possess many of the functions of both neutrophils (phagocytosis, degranulation) and platelets (ability to initiate clotting of hemolymph). In vertebrates, these frontline immune cells take the form of the classic neutrophil, a granular phagocyte that is rapidly recruited to sites of infection or injury. Diverging from its evolutionary roots, the vertebrate neutrophil has lost much of its hemostatic function and appears to be dedicated to the host response to infection/injury.In many ways, the rapid and robust response of neutrophils to infection has placed this leukocyte in the spotlight as the prototypical cell of the innate immune response. Upon infection or injury, neutrophils are recruited en masse, migrating from the bloodstream, crossing the endothelium, and entering the tissue interstitium where these cells then home to the specific site of challenge. Over the past century, these foot soldiers of the innate immune system have been studied in detail, providing great insight as to how the host recognizes pathogens, how cells are recruited to specific tissue beds, how immune cells are able to directly kill a variety of pathogens (lysosomes, proteases, reactive-oxygen species), and how immune cells inflict the collateral damage associated with inflammation. These studies began to define a clear role for the neutrophil as a short lived, non-discriminating killer that, while key to controlling infectious agents, often resulted in significant harm to self-tissues in an effort to ensure the clearance of the pathogen. For decades, this view of neutrophils as an unsophisticated Bthug^of the innate immune system predominated, and, for the most part, limited efforts to search for, and understand, other functions of the neutrophil.Despite the common view that we had already fully mapped the function of the neutrophil, research persisted and, with the advent of new techniques and technology (conditional genetic knock-out animals, blocking and depleting antibodies, multi-color flow cytometry, etc.), our understanding of these prototypical innate immune cells has changed dramatically over the last two decades. In particular, perhaps no single technique has advanced our understanding of neutrophils biology better than intravital imaging. What began with Julius Cohnheim nearly 150 years ago, using a simple white-light microscope to study blood flow and leukocyte behavior in a frog's tongue, has evolved to embrace cuttingedge technology allowing for the visualization multiple cell types, pathogens, and effector functions in real-time, in the living animal with resolution never believed to be possible. With this approach we have mapped cell recruitment, adhe...

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confidence: 99%

Neutrophils: multitasking first responders of immunity and tissue homeostasis

2018

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“…ROS production is activated by hypoxia, ischaemia, anoxia–reoxygenation, VEGF and Ang1 (Zhou et al., 2013). Equine endothelial cells have been shown to produce ROS in vitro when subjected to anoxia–reoxygenation (Anderson & Singh, 2018; de Rebiere de Pouyade et al., 2011).…”

Section: Endothelial Regulatory Molecules In Equine Angiogenesismentioning

confidence: 99%

Endothelial cells and angiogenesis in the horse in health and disease—A review

Rieger

Kaessmeyer

Masri

et al. 2020

Anat Histol Embryol

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The cardiovascular system is the first functional organ in the embryo, and its blood vessels form a widespread conductive network within the organism. Blood vessels develop de novo, by the differentiation of endothelial progenitor cells (vasculogenesis) or by angiogenesis, which is the formation of new blood vessels from existing ones. This review presents an overview of the current knowledge on physiological and pathological angiogenesis in the horse including studies on equine endothelial cells. Principal study fields in equine angiogenesis research were identified: equine endothelial progenitor cells; equine endothelial cells and angiogenesis (heterogeneity, markers and assessment); endothelial regulatory molecules in equine angiogenesis; angiogenesis research in equine reproduction (ovary, uterus, placenta and conceptus, testis); angiogenesis research in pathological conditions (tumours, ocular pathologies, equine wound healing, musculoskeletal system and laminitis). The review also includes a table that summarizes in vitro studies on equine endothelial cells, either describing the isolation procedure or using previously isolated endothelial cells. A particular challenge of the review was that results published are fragmentary and sometimes even contradictory, raising more questions than they answer. In conclusion, angiogenesis is a major factor in several diseases frequently occurring in horses, but relatively few studies focus on angiogenesis in the horse. The challenge for the future is therefore to continue exploring new therapeutic angiogenesis strategies for horses to fill in the missing pieces of the puzzle.

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“…Neutrophils, the most abundant and important cell component of the innate immune system play a major role in host defense as the first cellular type to be recruited to fight infection and inflammation (1,2). They are the most abundant leukocytes in circulation and are first recruited to the infected sites.…”

Section: Introductionmentioning

confidence: 99%

Tamoxifen triggers the in vitro release of neutrophil extracellular traps in healthy horses

et al. 2023

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Neutrophils display an array of biological functions including the formation of neutrophil extracellular traps (NETs), web-like structures specialized in trapping, neutralizing, killing and preventing microbial dissemination within the host. However, NETs contribute to a number of inflammatory pathologies, including severe equine asthma. Tamoxifen (TX) is a selective estrogen receptor modulator which belongs to the triphenylethyllenes group of molecules, and which is used as a treatment in all stages of estrogen-positive human breast cancer. Our previous results suggest that tamoxifen can modulate neutrophil functionality and promote resolution of inflammation; this would partly explain the clinical beneficial effect of this drug in horses with airway inflammation. Enhanced NETs production has been reported with tamoxifen use in humans, but minimal data exists regarding the drug's effect on NETs in horses. The aim of this study is to assess the in vitro effect of TX on NETs formation from peripheral blood of healthy horses. Five clinically healthy mixed-breed adult horses were enrolled in the study. For this, cellular free DNA quantification, immunofluorescence for the visualization of NETs, assessment of different types of NETs, and detection of mitochondrial superoxide. TX induced NETs formation at a concentration of 10 uM. Our results show that only two types of NETs were induced by TX: 95% spread NETs (sprNETs) and 5% aggregated NETs (aggNETs). Furthermore, induction of these NETs could be influenced by mitochondrial ROS. Future research should involve an In vivo study of horses with severe asthma and TX treatment, to evaluate BALF neutrophil NET formation. In conclusion, this in vitro study suggests that the resolution of inflammation by TX in horses with airway inflammation is due to inhibition of other neutrophilic functions but not to NET formation.

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Equine neutrophils and their role in ischemia reperfusion injury and lung inflammation

Cited by 12 publications

References 84 publications

Neutrophils: multitasking first responders of immunity and tissue homeostasis

Neutrophils: multitasking first responders of immunity and tissue homeostasis

Endothelial cells and angiogenesis in the horse in health and disease—A review

Tamoxifen triggers the in vitro release of neutrophil extracellular traps in healthy horses

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