Regulation of chemokine expression by cyclosporine a in alveolar macrophages exposed to hypoxia and reoxygenation

Naidu, Babu; Krishnadasan, Baiya; Byrne, Karen; Farr, Angie; Rosengart, Matthew; Verrier, Edward D.; Mulligan, Michael S.

doi:10.1016/s0003-4975(02)03746-3

Cited by 45 publications

(45 citation statements)

References 22 publications

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“…It is known that macrophages can be activated by many stimuli, including low O 2 tension (33,43), resulting in expression of various inflammatory cytokines and chemokines (4,9,25,36). The important role of macrophages in I/R injury has been demonstrated in the liver, gut, and heart (6,23,44).…”

Section: Discussionmentioning

confidence: 99%

“…In human lung transplantation, TNF-␣, interferon (IFN)-␥, interleukin (IL)-8, IL-10, IL-12, and other pro-and anti-inflammatory cytokines/ chemokines are elevated in the lung (11). In response to oxidative stress, AMs release proinflammatory cytokines and chemokines such as TNF-␣, IFN-␥, and MIP-2 (a rodent analog of IL-8) (9,36). Anti-TNF-␣ antibody pretreatment results in marked reduction of leukocyte infiltration and injury after lung I/R (24,26).…”

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confidence: 99%

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Alveolar macrophage activation is a key initiation signal for acute lung ischemia-reperfusion injury

Zhao¹,

Fernández²,

Doctor³

et al. 2006

American Journal of Physiology-Lung Cellular and Molecular Phys

170

146

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Alveolar macrophage activation is a key initiation signal for acute lung ischemia-reperfusion injury

Zhao¹,

Fernández²,

Doctor³

et al. 2006

American Journal of Physiology-Lung Cellular and Molecular Phys

170

146

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“…Cyclosporine A pretreatment is a very effective way to reduce reperfusion injury, because it decreases the alveolar macrophage response to hypoxia and reoxygenation (147).…”

Section: Therapeutic Possibilitiesmentioning

confidence: 99%

Lung ischemia-reperfusion injury: a molecular and clinical view on a complex pathophysiological process

Hengst

Gielis

Lin

et al. 2010

American Journal of Physiology-Heart and Circulatory Physiology

315

280

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Lung ischemia-reperfusion injury remains one of the major complications after cardiac bypass surgery and lung transplantation. Due to its dual blood supply system and the availability of oxygen from alveolar ventilation, the pathogenetic mechanisms of ischemia-reperfusion injury in the lungs are more complicated than in other organs, where loss of blood flow automatically leads to hypoxia. In this review, an extensive overview is given of the molecular and cellular mechanisms that are involved in the pathogenesis of lung ischemia-reperfusion injury and the possible therapeutic strategies to reduce or prevent it. In addition, the roles of neutrophils, alveolar macrophages, cytokines, and chemokines, as well as the alterations in the cell-death related pathways, are described in detail. pulmonary; lung transplantation; ventilated ischemia IN THE PAST, THE LUNG WAS thought to be relatively resistant to ischemia because of its dual circulation and the availability of oxygen from alveolar ventilation. However, the depletion of lung oxygenation by stopping the ventilation leads to the same degree of lung impairment as a decrease in mechanotransduction by loss of blood flow, as determined by increases in vascular pressure and permeability (11), indicating that any deficiency from oxygenation or mechanotransduction can have significant repercussions (149).Reperfusion of the ischemic lung is a double-edged sword. Reestablishing the perfusion of the ischemic lung is absolutely required to maintain the viability of the lung, but reperfusion itself can trigger a complex cascade of events, the so-called pulmonary ischemia-reperfusion injury (LIRI) (48), characterized by increased microvascular permeability (Pvasc), increased pulmonary vascular resistance (PVR), pulmonary edema, impaired oxygenation, and pulmonary hypertension. Ischemia of the lung, without loss of ventilation, results in a complex pathophysiological situation and, therefore, is not comparable with ischemia in other organs. During ventilated ischemia, for example, the adenosine triphosphate (ATP) levels remain normal while reactive oxygen species (ROS) are formed (70), illustrating aspects of complexity of the pathophysiology of ventilated and anoxic lung ischemia. Therefore, a distinction should be made between ventilated ischemia, meaning a loss of blood flow, and anoxia/reoxygenation, indicating the loss of oxygenation and/or perfusion. In this review, the terms anoxia/reoxygenation and ventilated ischemia will be used, if the specific model is known and/or the mechanism is suggested to be model specific. Ischemia alone will be used, if it applies for both mechanisms, if the specific model is not known, or the research involves other organs.Complete and prolonged lung anoxia for up to several hours is unavoidable during lung transplantation, with dire consequences. Reperfusion of the transplanted lung can lead to nonspecific alveolar damage, pulmonary edema, and hypoxemia within 72 h after lung transplantation. Even with the advancements in lung preservati...

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“…AMØ are a rich source of oxidants, cytokines, chemokines, growth factors, and arachidonic acid metabolites, which can be secreted in response to several stimuli, including hypoxia (16,20,21). Chemokines are primary products of activated AMØ (22).…”

Section: Clinical Relevancementioning

confidence: 99%

Monocyte Chemoattractant Protein–1 Released from Alveolar Macrophages Mediates the Systemic Inflammation of Acute Alveolar Hypoxia

Chao¹,

Donham²,

Rooijen³

et al. 2011

Am J Respir Cell Mol Biol

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Alveolar hypoxia produces rapid systemic inflammation in rats. Several lines of evidence suggest that the inflammation is not initiated by low systemic tissue partial pressure of oxygen (PO 2 ) but by a mediator released into the circulation by hypoxic alveolar macrophages. The mediator activates tissue mast cells to initiate inflammation. Monocyte chemoattractant protein-1/Chemokine (C-C motif) ligand 2 (MCP-1/CCL2) is rapidly released by hypoxic alveolar macrophages. This study investigated whether MCP-1 is the mediator of the systemic inflammation of alveolar hypoxia. Experiments in rats and in alveolar macrophages and peritoneal mast cells led to several results. (1) Alveolar hypoxia (10% O 2 breathing, 60 minutes) produced a rapid (5-minute) increase in plasma MCP-1 concentrations in conscious intact rats but not in alveolar macrophage-depleted rats. (2) Degranulation occurred when mast cells were immersed in the plasma of hypoxic intact rats but not in the plasma of alveolar macrophage-depleted rats. (3) MCP-1 added to normoxic rat plasma and the supernatant of normoxic alveolar macrophages produced a concentration-dependent degranulation of immersed mast cells. (4) MCP-1 applied to the mesentery of normoxic intact rats replicated the inflammation of alveolar hypoxia. (5) The CCR2b receptor antagonist RS-102895 prevented the mesenteric inflammation of alveolar hypoxia in intact rats. Additional data suggest that a cofactor constitutively generated in alveolar macrophages and present in normoxic body fluids is necessary for MCP-1 to activate mast cells at biologically relevant concentrations. We conclude that alveolar macrophage-borne MCP-1 is a key agent in the initiation of the systemic inflammation of alveolar hypoxia.Keywords: alveolar macrophages; alveolar hypoxia; systemic inflammation; monocyte chemoattractant protein-1; mast cells Alveolar hypoxia occurs in a number of clinical settings, and is frequently associated with systemic effects, some of which are thought to include an inflammatory component (1-5). The reduction of inspired partial pressure of oxygen (PO 2 ) in rats induces a rapid and widespread inflammatory response in the mesentery (6), skeletal muscle (7,8), and brain (9), as characterized by increased microvascular concentrations of reactive O 2 species (10), increased leukocyte endothelial adhesive interactions (6), leukocyte emigration (11), increased vascular permeability as evidenced by the extravasation of albumin in the presence of reduced blood flow (11-13), and the degranulation of perivascular mast cells (MCs) (7,8,14). The degranulation of MCs is a key event: the MC stabilizer cromolyn attenuates all of the markers of inflammation induced by alveolar hypoxia (14). MCs are abundant in the microcirculatory beds in which the inflammatory effects of hypoxia were demonstrated (15-17), and are known to degranulate and release various inflammatory mediators, including leukotriene B 4 and platelet activating factor, which were shown to participate in the systemic inflammation of hypo...

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Regulation of chemokine expression by cyclosporine a in alveolar macrophages exposed to hypoxia and reoxygenation

Cited by 45 publications

References 22 publications

Alveolar macrophage activation is a key initiation signal for acute lung ischemia-reperfusion injury

Alveolar macrophage activation is a key initiation signal for acute lung ischemia-reperfusion injury

Lung ischemia-reperfusion injury: a molecular and clinical view on a complex pathophysiological process

Monocyte Chemoattractant Protein–1 Released from Alveolar Macrophages Mediates the Systemic Inflammation of Acute Alveolar Hypoxia

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