Role of substance P and the neurokinin 1 receptor in acute pancreatitis and pancreatitis-associated lung injury

Bhatia, Madhav; Saluja, Ashok K.; Hofbauer, B.; Frossard, Jean Louis; Lee, Hong Sik; Castagliuolo, Ignazio; Wang, Chi Chung; Gerard, Norma P.; Pothoulakis, Charalabos; Steer, Michael L.

doi:10.1073/pnas.95.8.4760

Cited by 276 publications

(283 citation statements)

References 28 publications

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“…In humans, substance P also appears to be important in neutrophil chemotaxis, mediating neutrophil binding to epithelial and endothelial cells and inducing release of cytokines, such as IL-8 (45). NK-1 receptor knockout mice have shown the importance of substance P in mediating neutrophil accumulation in pancreatitis and inflamed skin (46,47).…”

Section: Discussionmentioning

confidence: 99%

Activation of Neurokinin-1 Receptors during Ozone Inhalation Contributes to Epithelial Injury and Repair

Oslund¹,

Hyde

Putney³

et al. 2008

Am J Respir Cell Mol Biol

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We investigated the importance of neurokinin (NK)-1 receptors in epithelial injury and repair and neutrophil function. Conscious Wistar rats were exposed to 1 ppm ozone or filtered air for 8 hours, followed by an 8-hour postexposure period. Before exposure, we administered either the NK-1 receptor antagonist, SR140333, or saline as a control. Ethidium homodimer was instilled into lungs as a marker of necrotic airway epithelial cells. After fixation, whole mounts of airway dissected lung lobes were immunostained for 5-bromo-29-deoxyuridine, a marker of epithelial proliferation. Both ethidium homodimer and 5-bromo-29-deoxyuridine-positive epithelial cells were quantified in specific airway generations. Rats treated with the NK-1 receptor antagonist had significantly reduced epithelial injury and epithelial proliferation compared with control rats. Sections of terminal bronchioles showed no significant difference in the number of neutrophils in airways between groups. In addition, staining ozone-exposed lung sections for active caspase 3 showed no apoptotic cells, but ethidium-positive cells colocalized with the orphan nuclear receptor, Nur77, a marker of nonapoptotic, programmed cell death mediated by the NK-1 receptor. An immortalized human airway epithelial cell line, human bronchial epithelial-1, showed no significant difference in the number of oxidant stresspositive cells during exposure to hydrogen peroxide and a range of SR140333 doses, demonstrating no antioxidant effect of the receptor antagonist. We conclude that activation of the NK-1 receptor during acute ozone inhalation contributes to epithelial injury and subsequent epithelial proliferation, a critical component of repair, but does not influence neutrophil emigration into airways.

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Section: Discussionmentioning

confidence: 99%

Activation of Neurokinin-1 Receptors during Ozone Inhalation Contributes to Epithelial Injury and Repair

Oslund¹,

Hyde

Putney³

et al. 2008

Am J Respir Cell Mol Biol

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“…In addition to its known effects in nociception, it also has proinflammatory roles [85], and absence or inhibition of this receptor is protective against ALI [86][87][88]. Hydrogen sulfide (H 2 S) has also recently been shown to be an important mediator of inflammatory responses and may induce the production or release of substance P [89,90].…”

Section: Release Of Other Proinflammatory Mediatorsmentioning

confidence: 99%

Role of the pulmonary epithelium and inflammatory signals in acute lung injury

Manicone¹

2009

Expert Review of Clinical Immunology

113

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Acute lung injury (ALI) is a clinical disease marked by respiratory failure due to disruption of the epithelial and endothelial barrier, flooding of the alveolar compartment with protein-rich fluid and recruitment of neutrophils into the alveolar space. ALI affects approximately 200,000 patients annually in the USA and results in approximately 75,000 deaths. It is associated with prolonged mechanical ventilation, intensive medical care, high morbidity and mortality, and rising healthcare costs. Owing to its impact on public health, great strides have been made towards understanding the pathobiology of ALI to affect outcome. This review will focus on the role of the epithelial cell in the pathogenesis and resolution of ALI and the role of various inflammatory mediators in ALI. Keywordsβ2-agonist; acute lung injury; acute respiratory distress syndrome; chemokine; cytokine; epithelial cell; inflammation; methylprednisolone; neutrophil; salbutamol; steroid; ventilator-induced lung injuryAcute lung injury/acute respiratory distress syndrome (ALI/ARDS) was first described in 1967 by Ashbaugh and colleagues in a group of 12 patients who shared a constellation of clinical symptoms including acute respiratory distress, hypoxemia refractory to supplemental oxygen, decreased lung compliance and diffuse pulmonary infiltrates [1]. Since this first description, the clinical criteria have evolved to include acute onset of respiratory distress, bilateral pulmonary infiltrates seen on chest radiographs, absence of left-sided heart failure and hypoxemia, with the severity of hypoxemia distinguishing ALI and ARDS (Box 1) [2]. Extrapolating from recent epidemiologic studies using these criteria, ALI affects about 200,000 patients annually in the USA and results in approximately 75,000 deaths [3]. This disease, which can be caused by common events such as pneumonia, sepsis and trauma, results in high morbidity, mortality and healthcare expenditures associated with prolonged mechanical ventilation and intensive care. Because of its impact on public health and patient outcomes, great strides have been made towards understanding the pathobiology of ALI.When defined broadly to include all processes related to defense against microbes, other environmental insults and injury, a wide variety of cell types and proteins participate in inflammation and immunity. Leukocytes are the paradigmatic inflammatory cell type, but they are not the only cells that function in defense and immunity. The epithelial lining of all tissues forms a continuous barrier to the environment and is the first line of defense against infectious agents and toxins. Though specialized to serve distinct functions among tissues, epithelial cells respond similarly to injury and infection, and regulate leukocyte influx through the production of proinflammatory cytokines, chemokines and other factors that modulate chemokine gradients and effect leukocyte migration. This review will focus on the role of the pulmonary epithelium and inflammatory mediators in ALI. More s...

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“…Substance P (SP) and calcitonin generelated peptide (CGRP) are neurotransmitters that are released from these sensitive neurons, which seem to account for neurogenic inflammation in the pancreas. They can interact with endothelial cells, arterioles, mast cells and other immune cells to induce vasodilation, edema and inflammatory cell infiltration [38] . Concerning SP, it has been shown to play an important role in many inflammatory states [38] .…”

Section: Neurogenic Inflammation In Apmentioning

confidence: 99%

Cardiocirculatory pathophysiological mechanisms in severe acute pancreatitis

García

Calvo²

2010

WJGPT

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Acute pancreatitis (AP) is a common and potentially lethal acute inflammatory process. Although the majority of patients have a mild episode of AP, 10%-20% develop a severe acute pancreatitis (SAP) and suffer systemic inflammatory response syndrome (SIRS) and/or pancreatic necrosis. The main aim of this article is to review the set of events, first localized in the pancreas, that lead to pancreatic inflammation and to the spread to other organs contributing to multiorganic shock. The early pathogenic mechanisms in SAP are not completely understood but both premature activation of enzymes inside the pancreas, related to an impaired cytosolic Ca 2+ homeostasis, as well as release of pancreatic enzymes into the bloodstream are considered important events in the onset of pancreatitis disease. Moreover, afferent fibers within the pancreas release neurotransmitters in response to tissue damage. The vasodilator effects of these neurotransmitters and the activation of pro-inflammatory substances play a crucial role in amplifying the inflammatory response, which leads to systemic manifestation of AP. Damage extension to other organs leads to SIRS, which is usually associated with cardiocirculatory physiology impairment and a hypotensive state. Hypotension is a risk factor for death and is associated with a significant hyporesponsiveness to vasoconstrictors. This indicates that stabilization of the patient, once this pathological situation has been established, would be a very difficult task. Therefore, it seems particularly necessary to understand the pathological mechanisms involved in the first phases of AP to avoid damage beyond the pancreas. Moreover, efforts must also be directed to identify those patients who are at risk of developing SAP.

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Role of substance P and the neurokinin 1 receptor in acute pancreatitis and pancreatitis-associated lung injury

Cited by 276 publications

References 28 publications

Activation of Neurokinin-1 Receptors during Ozone Inhalation Contributes to Epithelial Injury and Repair

Activation of Neurokinin-1 Receptors during Ozone Inhalation Contributes to Epithelial Injury and Repair

Role of the pulmonary epithelium and inflammatory signals in acute lung injury

Cardiocirculatory pathophysiological mechanisms in severe acute pancreatitis

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