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Adhesion molecules contribute to ischemia and reperfusion-induced injury in the isolated rat lung
T M Moore1, P Khimenko, W K Adkins
1Department of Physiology, University of South Alabama, Mobile 36688, USA.
Abstract:
Leukocyte adherence to the endothelium after ischemia and reperfusion contributes to microvascular injury in most organs. The purpose of this study was to evaluate the leukocyte and endothelial cell adhesion molecules involved with ischemia-reperfusion (I/R)-induced pulmonary microvascular injury in the isolated rat lung. After 45 min of ischemia and 30 min of reperfusion, microvascular permeability was significantly increased and lung retention of leukocytes occurred. Pretreatment with monoclonal antibodies against the leukocyte adhesion molecule CD18 or the endothelial cell adhesion molecules intercellular adhesion molecule 1 and P-selectin significantly attenuated the I/R-induced permeability increase and lung sequestration of neutrophils, mononuclear leukocytes, and eosinophils. In contrast, immunoneutralization of the rat leukocyte adhesion molecule L-selectin neither protected against the I/R-induced permeability increase nor prevented lung sequestration of neutrophils and eosinophils. We conclude that leukocyte adherence in the pulmonary, microvasculature and subsequent permeability increase after I/R is dependent on the integrin CD18, its endothelial cell ligand intercellular adhesion molecule 1, and the endothelial cell rolling factor P-selectin but not the leukocyte rolling factor L-selectin.
Insights
Leukocyte adherence molecules CD18, ICAM-1, and P-selectin are key in ischemia-reperfusion lung injury. Blocking these molecules reduced leukocyte buildup and microvascular permeability in rat lungs.
Area of Science:
- Pulmonary Medicine
- Immunology
- Vascular Biology
Background:
- Leukocyte adherence to endothelium contributes to microvascular injury following ischemia and reperfusion (I/R) in various organs.
- Understanding the specific adhesion molecules involved in I/R-induced pulmonary microvascular injury is crucial for developing targeted therapies.
Purpose of the Study:
- To evaluate the roles of leukocyte and endothelial cell adhesion molecules in ischemia-reperfusion (I/R)-induced pulmonary microvascular injury.
- To determine the specific molecular mechanisms underlying leukocyte sequestration and microvascular permeability changes in the isolated rat lung model.
Main Methods:
- Isolated rat lung model subjected to 45 minutes of ischemia followed by 30 minutes of reperfusion.
- Administration of monoclonal antibodies targeting leukocyte adhesion molecule CD18, endothelial cell adhesion molecules intercellular adhesion molecule 1 (ICAM-1) and P-selectin, and rat leukocyte adhesion molecule L-selectin.
- Assessment of microvascular permeability and leukocyte sequestration (neutrophils, mononuclear leukocytes, eosinophils) within the lung.
Main Results:
- Ischemia-reperfusion significantly increased microvascular permeability and led to leukocyte retention in the lungs.
- Pretreatment with antibodies against CD18, ICAM-1, and P-selectin significantly reduced I/R-induced permeability and leukocyte sequestration.
- Immunoneutralization of L-selectin did not provide protection against I/R-induced permeability increases or leukocyte sequestration.
Conclusions:
- Leukocyte adherence in pulmonary microvasculature and subsequent permeability increase after I/R are critically dependent on the integrin CD18, its ligand ICAM-1, and P-selectin.
- L-selectin does not play a significant role in mediating I/R-induced pulmonary microvascular injury.
- Targeting CD18, ICAM-1, and P-selectin represents a potential therapeutic strategy for mitigating ischemia-reperfusion injury in the lungs.