The Impact Of Simulated Microgravity In Endothelial Cell Adhesion Molecule And PKC Signal Pathway

Many spaceflights have confirmed that astronauts experienced decreased immunity andvulnerabile to infection in microgravity. In immune response, leukocytes require cell adhesionmolecules (CAMs) both on their membrane and endothelial cells (ECs) to transmigratethrough the endothelium, and reach the infected sites. Intercellular adhesionmolecule-1(ICAM-1) and vascular cell adhesion molecule-1(VCAM-1), both regarded as keyCAMs in EC, play a very crucial role in leukocytes transendothelial migration. By usingNASA’ Rotary Cell Culture System(RCCS) to simulate microgravity(MG) and activatingHuman umbilical vein endothelial cell(HUVEC) with low concentration(10ng/mL) TNF-α,expression of ICAM-1and VCAM-1on cell membrane, distribution of ICAM-1on cellmembrane and cytoplasm, structure of cytoskeleton and transcription of ICAM-1andVCAM-1mRNA are detected by flow cytometry, laser scanning confocal microscope andRT-PCR respectively. We find that MG can lead to a remarkable increased expression ofICAM-1, but no significant change was found in VCAM-1. Also, disturbed cytoskeletonstructure and clustering of ICAM-1on cell membrane were observed in short times (rotationby5min,30min and1hour); however, after24hs clinorotation, cell cytoskeletonrearrangement was initiated. Compared with controls, MG group ICAM-1mRNA was notmanifest after5min, upregulated after30min, and after24hs it returns to the controls’ level.VCAM-1mRNA in MG group was downregulated after5min clinorotation, upregulated after30min, and equal to the control level after24hs clinorotation. Finally, PKC phosphorylationwas inhibited in MG. All these results can illustrate that MG can increase ICAM-1expressionand disorder of F-actin cytoskeleton, yet ECs may have a feedback way to regulate, which canresults in that ICAM-1mRNA was return to the same level of controls, as well as cytoskeletonwill reorganized.