Monocyte adhesion to endothelial cells increases with hind-limb unloading in rats

Introduction: Hind-limb unloading (HU) in rodents has been used as a model to simulate some effects of spaceflight on the musculoskeletal, cardiovascular, and immune systems in humans. HU leads to redistribution of extracellular fluid to the upper half of the body. We hypothesized that altered blood flow might induce intercellular adhesion molecule-1 (ICAM-1) expression of arterial endothelial cells and increase monocyte-endothelial adhesion. Methods: Male Sprague-Dawley rats were randomly assigned to either a control, 7-d HU, or 28-d HU group. The expression of ICAM-1 and monocyte adhesion was determined by immunohistochemistry. Results: In control rats, ICAM-1 was not expressed in all vessels studied. HU induced the ICAM-1 expression in the carotid artery and thoracic aorta, but did not in the femoral artery. Staining density of ICAM-1 expression was stronger in the 28-d HU group than in the 7-d HU group. Endothelial-monocyte adhesion was significantly increased in the carotid artery and thoracic aorta from the HU groups compared with the control group, but completely absent in the femoral arteries of both the HU and control groups. In the thoracic aorta, but not in the carotid artery, endothelial-monocyte adhesion was more increased after 28-d HU than after 7-d HU. Conclusion: These data indicate that an increase in shear stress induced by HU stimulates ICAM-1 expression on arteries, which contributes to adhesion of monocytes on their endothelium. Reduced shear stress has no effects on monocyte adehsion.