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Related Concept Videos

Chronic Pancreatitis I: Introduction01:24

Chronic Pancreatitis I: Introduction

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The pancreas, an elongated and flat gland situated behind the stomach, serves a vital function in digesting food and managing blood sugar levels.
Pancreatitis is the inflammation of the pancreas, which occurs when the immune system becomes active and causes swelling, pain, and disruptions in organ function. Pancreatitis can manifest as either an acute or chronic condition.
Acute pancreatitis arises suddenly and lasts for a brief duration, while chronic pancreatitis is a long-term affliction...
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Acute Pancreatitis I: Introduction01:27

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Pancreatitis is inflammation of the pancreas, an organ located behind the stomach. It can be either acute or chronic.
Acute pancreatitis is characterized by rapid inflammation of the pancreas, often caused by factors like gallstone blockage or excessive alcohol consumption. Chronic pancreatitis, on the other hand, is a slow, progressive inflammation that may result from long-term alcohol abuse, obstructions in the pancreatic duct, or genetic factors.
The causes of acute pancreatitis include:
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Acute Pancreatitis II: Clinical Manifestations and Management01:30

Acute Pancreatitis II: Clinical Manifestations and Management

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Acute pancreatitis presents a complex medical emergency characterized by rapid onset inflammation of the pancreas, demanding timely diagnosis and management to prevent complications. The condition primarily manifests through severe upper abdominal pain that often radiates to the back. This pain intensifies following the consumption of fatty foods. Accompanying symptoms such as nausea, vomiting, abdominal distention, fever, dyspnea, cyanosis, and jaundice can vary in intensity but significantly...
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Nitric Oxide Signaling Pathway01:28

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Nitric oxide (NO), an inorganic gas, acts as a potent second messenger in most animal and plant tissues. NO diffuses out of the cells that produce it and enters the neighboring cells to generate a downstream response. NO synthase (NOS) catalyzes NO production by the deamination of the amino acid arginine. There are three isoforms of NOS. Endothelial cells have endothelial NOS (eNOS), nerve and muscle cells have neuronal NOS (nNOS), and macrophages produce inducible NOS (iNOS) upon exposure...
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Neutrophil-specific ORAI1 Calcium Channel Inhibition Reduces Pancreatitis-associated Acute Lung Injury.

Mengya Niu1,2, Xiuli Zhang3,4, Zengkai Wu2

  • 1School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China.

Function (Oxford, England)
|November 29, 2023
PubMed
Summary

Store-operated Ca2+ entry (SOCE) via ORAI1 channels in neutrophils, not pancreatic cells, drives acute lung injury during pancreatitis. Targeting neutrophils offers a promising therapeutic strategy for pancreatitis-associated lung damage.

Keywords:
ORAI1acute lung injuryearly treatmentneutrophils

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Area of Science:

  • Immunology
  • Cell Biology
  • Gastroenterology

Background:

  • Acute pancreatitis involves pancreatic inflammation and systemic responses, often leading to organ injury.
  • Store-operated Ca2+ entry (SOCE) through ORAI1 channels is implicated in pancreatitis initiation.
  • The role of ORAI1 in pancreatitis-associated acute lung injury remains unclear.

Purpose of the Study:

  • To investigate the specific cell types and mechanisms of ORAI1 involvement in acute pancreatitis and associated lung injury.
  • To determine whether ORAI1 in pancreatic acinar cells or neutrophils is critical for lung injury.
  • To evaluate the therapeutic potential of targeting ORAI1 in different cell types.

Main Methods:

  • Utilized mice with pancreas-specific and neutrophil-specific deletion of ORAI1.
  • Assessed pancreatic tissue damage, immune cell infiltration, and lung injury markers.
  • Examined neutrophil functions including Ca2+ influx, chemotaxis, reactive oxygen species production, and neutrophil extracellular trap formation.

Main Results:

  • Pancreas-specific ORAI1 deletion protected against pancreatic damage but not lung injury.
  • Neutrophil-specific ORAI1 deletion protected against lung injury and cytokine release in pancreatitis and sepsis models.
  • Orai1 deletion in neutrophils impaired key neutrophil functions, including Ca2+ influx and chemotaxis.

Conclusions:

  • Neutrophil ORAI1, not pancreatic ORAI1, is essential for pancreatitis-associated acute lung injury.
  • Distinct cell-type contributions to pancreatic versus systemic injury highlight therapeutic targets.
  • Multicellular targeting strategies may be more effective for treating acute pancreatitis and its complications.