Cytotoxic effects of peroxynitrite, polymorphonuclear neutrophils, free-radical scavengers, inhibitors of myeloperoxidase, and inhibitors of nitric oxide synthase on bovine mammary secretory epithelial cells

Ledbetter, T.K; Paape, Max; Douglass, Larry W.

doi:10.2460/ajvr.2001.62.286

Cited by 25 publications

(15 citation statements)

References 42 publications

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“…PMA-activated neutrophils in combination with E. coli endotoxins caused release of superoxide. Epithelial damage was also observed [22,135]. Melatonin that scavenges hydroxyl radicals and peroxynitrite reduced neutrophil-induced cytotoxicity dose-dependently [22].…”

Section: Cytotoxic Mediatorsmentioning

confidence: 95%

“…Host lipid peroxidation, initiated by enzymes such as NADPH oxidase and myeloperoxidase, occurs [260]. (2) Neutrophilic degranulation, during which release of proteases occurs as a result of neutrophil trafficking or as a consequence of their phagocytic activity, was also shown to be cytotoxic [2,22,38,135,165,172]. During phagocytosis lysosomes migrate toward the particle being internalised and lysosomal enzymes are released before fusion of the pseudopodia is completed, resulting in the release of lysosomal contents to the outside of the PMN [81].…”

Section: Cytotoxic Mediatorsmentioning

confidence: 99%

“…Together, histidine and 500 000 activated PMN/mL were also toxic [135]. As a consequence, the effect of antioxidants was investigated on the neutrophil induced epithelial damage in vitro.…”

Section: Cytotoxic Mediatorsmentioning

confidence: 99%

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Severity of E. coli mastitis is mainly determined by cow factors

et al. 2003

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-Intramammary infections of dairy cows with Gram-positive bacteria such as Staphylococcus aureus (major cause of mastitis) have received a lot of attention because of their major economic impact on the dairy farm through production losses induced by an increase in somatic cell count. Management strategies, including greater awareness for efficient milking and hygienic measures, have limited the spread of Gram-positive bacteria and resulted in a significant decrease of proportion of S. aureus isolates and subclinical mastitis worldwide. Other organisms such as coliform subspecies and Streptococcus uberis, both environmental bacteria that cause clinical mastitis, have received less attention. Escherichia coli causes inflammation of the mammary gland in dairy cows around parturition and during early lactation with striking local and sometimes severe systemic clinical symptoms. This disease affects many high producing cows in dairy herds and may cause several cases of death per year in the most severe cases. It is well known that bacterial, cow and environmental factors are interdependent and influence mastitis susceptibility. Many studies, executed during the last decade, indicate that the severity of E. coli mastitis is mainly determined by cow factors rather than by E. coli pathogenicity. During E. coli mastitis, the host defense status is a cardinal factor determining the outcome of the disease. Today, we know that the neutrophil is a key factor in the cows' defense against intramammary infection with E. coli. Effective elimination of the pathogen by neutrophils is important for the resolution of infection and the outcome of E. coli mastitis. This review is a compilation of some major findings over the last 15 years concerning mainly host factors that modulate and influence neutrophil function and the mammary inflammatory reaction. The individual chapters address: virulence factors of E. coli strains, how neutrophils kill E. coli, connection between endotoxins, tumor necrosis factor-a and nitric oxide, severity classification of E. coli mastitis, lifespan of neutrophils, host factors that influence severity, tissue damage and production loss.

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Section: Cytotoxic Mediatorsmentioning

confidence: 95%

Section: Cytotoxic Mediatorsmentioning

confidence: 99%

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Severity of E. coli mastitis is mainly determined by cow factors

et al. 2003

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“…Although PMN provide a beneficial effect by eliminating the infectious agent, prolonged exposure of mammary tissue to PMN results in injury to secretory epithelium [29]. One mechanism by which this may occur is through release of toxic oxygen radicals and proteases, agents which are both bactericidal and cytotoxic to host tissue [96,181]. Prolonged inflammation resulting in injury to the mammary secretory epithelium results in scarring and leads to a permanent decrease in milk production [165].…”

Section: Regulation Of Pmn Life Spanmentioning

confidence: 99%

“…Because onset of apoptosis leads to functional impairment of bovine PMN [176], in vivo administration of caspase inhibitors may play an effective role in enhancing the ability of PMN to respond to intramammary infection. Further, caspase inhibitors may have the additional benefit of protecting secretory epithelium from deleterious effects of PMN-derived cytotoxic mediators produced in response to infection [29,96]. In support of a potential therapeutic benefit for caspase inhibitors in mastitis, two studies have shown that prevention of lymphocyte-induced apoptosis with the caspase inhibitor z-VAD enhances survival in a murine model of sepsis [76,77].…”

Section: Cellular Regulation Of Apoptosismentioning

confidence: 99%

The bovine neutrophil: Structure and function in blood and milk

Paape¹,

Bannerman²,

et al. 2003

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-Migration of polymorphonuclear neutrophil leukocytes (PMN) into the mammary gland provide the first line of defense against invading mastitis pathogens. Bacteria release potent toxins that activate white blood cells and epithelial cells in the mammary gland to secrete cytokines that recruit PMN that function as phagocytes at the site of infection. While freshly migrated PMN are active phagocytes, continued exposure of PMN to inhibitory factors in milk such as fat globules and casein, leads to altered PMN morphology and reduced phagocytosis. In the course of phagocytosing and destroying invading pathogens, PMN release chemicals that not only kill the pathogens but that also cause injury to the delicate lining of the mammary gland. This will result in permanent scarring and reduced numbers of milk secretory cells. The life span of PMN is limited by the onset of apoptosis. To minimize damage to mammary tissue, PMN undergo a specialized process of programmed cell death known as apoptosis. Macrophages quickly engulf and phagocytose apoptotic PMN, thereby minimizing the release of PMN granular contents that are damaging to tissue. The PMN possess an array of cell surface receptors that allow them to adhere and migrate through endothelium and to recognize and phagocytose bacteria. One receptor found on phagocytes that is receiving considerable attention in the control of infections by Gram-negative bacteria is CD14. Binding of lipopolysaccharide (LPS) to membrane bound CD14 causes release of tumor necrosis factor-a and sepsis. Binding of LPS to soluble CD14 shed from CD14-bearing cells results in neutralization of LPS and rapid recruitment of PMN to the site of infection. Recent advances in the fields of genomics and proteomics should greatly enhance our understanding of the PMN role in controlling intramammary infections in ruminants. Further, manipulation of PMN, through either recombinant proteins such as soluble CD14 that enhance PMN response or agents that mediate PMN apoptosis, may serve as novel therapeutics for the treatment of mastitis.

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Noscapine‐Loaded Nanostructured Lipid Carriers as a Potential Topical Delivery to Bovine Mastitis Treatment

et al. 2020

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Noscapine (NO) is a lipophilic benzylisoquinoline alkaloid with antioxidant, antitussive and anti-cancer properties. This study aimed to incorporate this alkaloid into an innovative topical gel-based on nanostructured lipid carrier (NLCs) to facilitate its incorporation and distribution into the organism to bovine mastitis treatment. Drug release studies were carried out using square wave voltammetry (SWV) as an alternative technique. The NLCs showed a 100 % encapsulation efficiency and, a fast release profile, releasing 86.7 % of the incorporated NO in 5 hours.On the other hand, the lipid nanoparticles' stability was analyzed using SWV and transmission electron microscope techniques. For these studies, NLCs with and without NO incorporated were immobilized onto a carbon paste electrode and exposed to free radicals attack. The stability studies were assisted with dynamic light scattering. The results reveal a promising alternative drug delivery system for NO topical application.[a] Dr.

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Cytotoxic effects of peroxynitrite, polymorphonuclear neutrophils, free-radical scavengers, inhibitors of myeloperoxidase, and inhibitors of nitric oxide synthase on bovine mammary secretory epithelial cells

Abstract: Peroxynitrite, MPO, and histidine are toxic to mammary secretory epithelial cells. Superoxide dismutase and inhibition of MPO activity mitigate these effects. Nitration of MAC-T cell tyrosine residues may be positively associated with viability.

Cited by 25 publications

References 42 publications

Severity of E. coli mastitis is mainly determined by cow factors

Severity of E. coli mastitis is mainly determined by cow factors

The bovine neutrophil: Structure and function in blood and milk

Noscapine‐Loaded Nanostructured Lipid Carriers as a Potential Topical Delivery to Bovine Mastitis Treatment

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