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Polymorphonuclear leukocyte: arachidonate edema
Abstract:
Polymorphonuclear leukocytes (PMN) are important participants in many models of acute lung edema. Enhanced metabolism of arachidonate is also characteristic of many of these models. We found that PMN and arachidonate, but neither alone, increased alveolar capillary permeability of isolated perfused lungs and increased transfer of albumin across monolayers of endothelial cells cultured on micropore filters. Inhibition of PMN, but not endothelial cyclooxygenase, blunted the edematous process. Neither PMN proteases nor PMN-derived oxidants were involved. The edemagenic activity was not found in supernatants of PMN and arachidonate, and unstable prostaglandins did not alter endothelial albumin transfer. The edemagenic process was not inhibited by blocking leukotriene synthesis, and endothelial albumin transfer was not increased by direct addition of leukotrienes to endothelium. These data demonstrate that PMN and arachidonate can interact to increase endothelial permeability and that PMN cyclooxygenase activity is important for this process. This interaction is of potential significance to the acute inflammatory process in the lung vasculature.
Insights
Polymorphonuclear leukocytes (PMN) and arachidonate interact to increase lung vascular permeability. PMN cyclooxygenase activity is crucial for this edematous process, impacting acute lung inflammation.
Area of Science:
- Pulmonary Medicine
- Cell Biology
- Inflammation Research
Background:
- Polymorphonuclear leukocytes (PMN) and enhanced arachidonate metabolism are implicated in acute lung edema.
- Alveolar capillary permeability and endothelial barrier function are critical in lung fluid balance.
Purpose of the Study:
- To investigate the interaction between PMN and arachidonate in increasing alveolar capillary permeability.
- To determine the role of PMN cyclooxygenase activity in the edematous process.
Main Methods:
- Isolated perfused lungs and cultured endothelial cell monolayers were used to assess alveolar capillary permeability.
- Experiments involved the addition of PMN and arachidonate, with and without inhibitors of PMN or endothelial cyclooxygenase, proteases, and oxidants.
- Leukotriene synthesis inhibition and direct leukotriene addition were also tested.
Main Results:
- PMN and arachidonate together, but not alone, increased lung vascular permeability and albumin transfer across endothelial cells.
- Inhibition of PMN cyclooxygenase, but not endothelial cyclooxygenase, significantly reduced the edematous effect.
- PMN proteases, PMN-derived oxidants, and leukotrienes were not found to be directly involved in this specific edematogenic activity.
Conclusions:
- PMN and arachidonate interact to enhance endothelial permeability in the lung vasculature.
- PMN cyclooxygenase activity plays a critical role in mediating this PMN-arachidonate-induced increase in permeability.
- This interaction is a significant factor in acute inflammatory processes within the lung vasculature.