Adhesion molecules contribute to ischemia and reperfusion-induced injury in the isolated rat lung

Moore, Timothy M.; Khimenko, P. L.; Adkins, W. K.; Miyasaka, Masayuki; Taylor, Aubrey E.

doi:10.1152/jappl.1995.78.6.2245

Cited by 84 publications

(70 citation statements)

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“…To our knowledge, we provide the first direct evidence that high pressure induces P-selectin expression in lung microvessels, a finding that is relevant to mechanisms of lung injury. P-selectin is implicated in such mechanisms, because lung injury after complement activation or ischemia-reperfusion is attenuated by anti-P-selectin antibody (42,43). In stimulated endothe- lial cells, P-selectin is rapidly internalized (16) and either sorted to the Golgi (35) and WP bodies for receptor reexpression (44) or targeted to lysosomes in order to prevent recycling (36).…”

Section: Discussionmentioning

confidence: 99%

Pressure is proinflammatory in lung venular capillaries

Kuebler

Ying²,

Singh³

et al. 1999

J. Clin. Invest.

135

110

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Section: Discussionmentioning

confidence: 99%

Pressure is proinflammatory in lung venular capillaries

Kuebler

Ying²,

Singh³

et al. 1999

J. Clin. Invest.

135

110

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“…Evidence against this role includes findings that P-selectin-inhibitory mAb does not block leukocyte rolling in venules (26) and that bacteria-induced leukocyte migration is not inhibited in P/E-selectin-knockout mice (27). Evidence supporting a role for P-selectin includes findings that P-selectin-blocking mAbs inhibit ALI induced by cobra venom (28) or ischemia-reperfusion (29) and that P-selectin-knockout mice are protected from ALI due to ischemia-reperfusion (30). We reported that P-selectin accounts for the pressure-induced leukocyte accumulation (6), thereby implying a role for P-selectin in the proinflammatory phenotype induced by pulmonary venous hypertension.…”

Section: Mitochondrial Buffering It Is Proposed That Mitochondria Bumentioning

confidence: 99%

Connexin 43 mediates spread of Ca2+ -dependent proinflammatory responses in lung capillaries

Parthasarathi

Ichimura

Monma

et al. 2006

Journal of Clinical Investigation

144

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Acute lung injury (ALI), which is associated with a mortality of 30-40%, is attributable to inflammation that develops rapidly across the lung's vast vascular surface, involving an entire lung or even both lungs. No specific mechanism explains this extensive inflammatory spread, probably because of the lack of approaches for detecting signal conduction in lung capillaries. Here, we addressed this question by applying the photolytic uncaging approach to induce focal increases in Ca 2+ levels in targeted endothelial cells of alveolar capillaries. Uncaging caused Ca 2+ levels to increase not only in the targeted cell, but also in vascular locations up to 150 mm from the target site, indicating that Ca 2+ was conducted from the capillary to adjacent vessels. No such conduction was evident in mouse lungs lacking endothelial connexin 43 (Cx43), or in rat lungs in which we pretreated vessels with peptide inhibitors of Cx43. These findings provide the first direct evidence to our knowledge that interendothelial Ca 2+ conduction occurs in the lung capillary bed and that Cx43-containing gap junctions mediate the conduction. A proinflammatory effect was evident in that induction of increases in Ca 2+ levels in the capillary activated expression of the leukocyte adherence receptor P-selectin in venules. Further, peptide inhibitors of Cx43 completely blocked thrombin-induced microvascular permeability increases. Together, our findings reveal a novel role for Cx43-mediated gap junctions, namely as conduits for the spread of proinflammatory signals in the lung capillary bed. Gap junctional mechanisms require further consideration in the understanding of ALI.

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“…It is not well documented whether, at the same time, acute hypoxia also induces changes at the level of pulmonary inflammatory mediators. Most of the in vivo studies performed to date have concentrated on ischemia-reperfusion injury in organs (15,18). However, the direct effects of hypoxia without reperfusion on tissue have not been well explored.…”

mentioning

confidence: 99%

Decreased alveolar oxygen induces lung inflammation

Madjdpour

Jewell

Kneller

et al. 2003

American Journal of Physiology-Lung Cellular and Molecular Phys

178

133

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Molecular mechanisms of the inflammatory reaction in hypoxia-induced lung injury are not well defined. Therefore, effects of alveolar hypoxia were studied in rat lungs, exposing rats to 10% oxygen over periods of 1, 2, 4, 6, and 8 h. An increase in the number of macrophages in bronchoalveolar lavage fluid of hypoxic animals was shown between 1 and 8 h. Extravasation of albumin was enhanced after 1 h and remained increased throughout the study period. NF-κB-binding activity as well as mRNA for TNF-α, macrophage inflammatory protein (MIP)-1β, and monocyte chemoattractant protein (MCP)-1 were increased within the first 2 h of exposure to hypoxia. Hypoxia-inducible factor (HIF)-1α and intercellular adhesion molecule (ICAM)-1 mRNA were upregulated between 1 and 6 h. Elimination of alveolar macrophages by intratracheal application of liposome-encapsulated clodronate led to a decreased expression of NF-κB binding activity, HIF-1α, TNF-α, ICAM-1, and MIP-1β. In summary, alveolar hypoxia induced macrophage recruitment, an increase in albumin leakage, and enhanced expression of inflammatory mediators, which were mainly macrophage dependent. Alveolar macrophages appear to have a prominent role in the inflammatory response in hypoxia-induced lung injury and the related upregulation of inflammatory mediators.

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Adhesion molecules contribute to ischemia and reperfusion-induced injury in the isolated rat lung

Cited by 84 publications

References 0 publications

Pressure is proinflammatory in lung venular capillaries

Pressure is proinflammatory in lung venular capillaries

Connexin 43 mediates spread of Ca2+ -dependent proinflammatory responses in lung capillaries

Decreased alveolar oxygen induces lung inflammation

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