Depletion Of Pulmonary Intravascular Macrophages Rescues Inflammation-Induced Delayed Neutrophil Apoptosis In Horses

The objective of this study was to determine the effect of pulmonary intravascular macrophage depletion on systemic inflammation and ex vivo neutrophil apoptosis, using an experimental model of intestinal ischemia and reperfusion injury in horses. Neutrophils were isolated before and after surgery from horses that were randomized to 3 treatment groups: sham celiotomy (CEL, n=4), intestinal ischemia and reperfusion (IR, n=6), intestinal ischemia and reperfusion with gadolinium chloride treatment to deplete pulmonary intravascular macrophages (PIMs, IRGC, n=6). Neutrophil apoptosis was assessed with Annexin V and propidium iodide staining quantified with flow cytometry and caspase-3, -8, and -9 activities in neutrophil lysates. All horses experienced a systemic inflammatory response following surgery. Following surgery, ex vivo neutrophil apoptosis was significantly delayed after 12 or 24 h in culture, except in IRGC horses (12 h: CEL: P = 0.03, IR: P = 0.05, IRGC: P =0.2; 24 h: CEL: P = 0.001, IR: P = 0.004, IRGC: P = 0.3). Caspase-3, -8, and -9 activities were significantly reduced in neutrophils isolated after surgery and cultured for 12 h in IR horses, but not IRGC horses (IR caspase-3: P = 0.002, IR caspase-8: 0.002 P =, IR caspase-9: P = 0.04). Serum TNF-α concentration were increased in IRGC horses for 6-18 h following jejunal ischemia. Following surgery, ex vivo equine neutrophil apoptosis was delayed via down-regulation of caspase activity, which was ameliorated by PIM depletion potentially via upregulation of TNF-α.

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Effect of brefeldin A (BFA) on the unique surface coat of pulmonary intravascular macrophages (PIMs) of sheep: Ultrastructural and cytochemical study

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100145935 ◽

1993 ◽

Vol 51 ◽

pp. 18-19

Author(s):

Baljit Singh

Keyword(s):

Brefeldin A ◽

Ultrastructural Feature ◽

Surface Coat ◽

Anterograde Transport ◽

Cytochemical Study ◽

Active Involvement ◽

Electron Lucent ◽

Pulmonary Intravascular Macrophages ◽

Unique Surface

The PIM of sheep, calf, goat and horse has a characteristic ultrastructural feature in the form of a unique, heparin sensitive, globular surface coat present around the plasma membrane with an intervening electron lucent space of 32-40 nm. We previously showed the active involvement of this surface coat in the phagocytosis of tracer material like monastral blue and cationized ferritin. The surface coat is capable of reconstitution in vivo following disruption with heparin. The present study was aimed to investigate whether PIM is the source of surface coat or not. In the recent years the BFA has been extensively used to understand the secretory pathways in the cells because of its ability to cause a rapid and reversible block to the anterograde transport of proteins from the endoplasmic reticulum to the Golgi.Sheep (n=6) were weighed, their plasma volume was calculated indirectly and based on which a sufficient single intravenous dose of BFA was given so as to reach a concentration of 4-5 microgram/ml of plasma.

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Faculty Opinions recommendation of Mycobacterium tuberculosis inhibits neutrophil apoptosis, leading to delayed activation of naive CD4 T cells.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.13697956.15478096 ◽

2012 ◽

Author(s):

Mark Doherty

Keyword(s):

T Cells ◽

Mycobacterium Tuberculosis ◽

Cd4 T Cells ◽

Neutrophil Apoptosis

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Nitric Oxide in Life and Death of Neutrophils

Current Medicinal Chemistry ◽

10.2174/0929867326666181213093152 ◽

2019 ◽

Vol 26 (31) ◽

pp. 5764-5780 ◽

Cited By ~ 1

Author(s):

Svetlana I. Galkina ◽

Ekaterina A. Golenkina ◽

Galina M. Viryasova ◽

Yulia M. Romanova ◽

Galina F. Sud’ina

Keyword(s):

Nitric Oxide ◽

Cell Damage ◽

Protective Role ◽

Neutrophil Apoptosis ◽

High Biological Activity ◽

Life And Death ◽

Signalling Molecule ◽

Activated Neutrophils ◽

Cell Death Mechanisms ◽

Prostacyclin Synthase

Background: Nitric Oxide (NO) is a key signalling molecule that has an important role in inflammation. It can be secreted by endothelial cells, neutrophils, and other cells, and once in circulation, NO plays important roles in regulating various neutrophil cellular activities and fate. Objective: To describe neutrophil cellular responses influenced by NO and its concomitant compound peroxynitrite and signalling mechanisms for neutrophil apoptosis. Methods: Literature was reviewed to assess the effects of NO on neutrophils. Results: NO plays an important role in various neutrophil cellular activities and interaction with other cells. The characteristic cellular activities of neutrophils are adhesion and phagocytosis. NO plays a protective role in neutrophil-endothelial interaction by preventing neutrophil adhesion and endothelial cell damage by activated neutrophils. NO suppresses neutrophil phagocytic activity but stimulates longdistance contact interactions through tubulovesicular extensions or cytonemes. Neutrophils are the main source of superoxide, but NO flow results in the formation of peroxynitrite, a compound with high biological activity. Peroxynitrite is involved in the regulation of eicosanoid biosynthesis and inhibits endothelial prostacyclin synthase. NO and peroxynitrite modulate cellular 5-lipoxygenase activity and leukotriene synthesis. Long-term exposure of neutrophils to NO results in the activation of cell death mechanisms and neutrophil apoptosis. Conclusion: Nitric oxide and the NO/superoxide interplay fine-tune mechanisms regulating life and death in neutrophils.

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