Soluble CD146 is generated by ectodomain shedding of membrane CD146 in a calcium-induced, matrix metalloprotease-dependent process

Abstract

CD146 is a cell adhesion molecule localized at the endothelial junction and is involved in the control of cell cell cohesion. In this study, we showed that calcium influx in human microvascular lung endothelial cells results in the loss of surface CD146 and the release of soluble CD146. This calcium induced CD146 shedding could be prevented with inhibitors of matrix metalloproteases indicating a central role of matrix metalloproteases in this process. We also investigated if CD146 shedding influences vascular permeability. Endothelial cell monolayers cultured on filter membranes showed an increased permeability for albumin when stimulated with ionomycin. This calcium induced increase in permeability was inhibited when CD146 shedding was prevented by a matrix metalloprotease inhibitor. Our data indicate that surface CD146 plays a central role in the regulation of vascular permeability and demonstrate that CD146 and matrix metalloproteases are potential targets to modify endothelial barrier function.

Effect of chronic intermittent hypoxia on triglyceride uptake in different tissues

“…CD146+ CD11b Ϫ cells were responsible for the vast majority of TG uptake in the lung. CD146 is a validated marker of pulmonary microvascular endothelial cells (38)(39)(40)(41). Therefore, our data strongly suggest that pulmonary microvascular endothelial cells participate in postprandial TG clearance.…”

“…3 and 4 ), we attempted to identify the cellular populations involved. We used CD11b as a macrophage marker ( 36,37 ) and CD146 as an endothelial cell marker (38)(39)(40)(41) in single-cell suspension of the lungs from mice…”

Up-Regulation of MUC18 in Airway Epithelial Cells by IL-13

“…In physiological conditions, MUC18 is considered as an intercellular adhesion molecule of cells like endothelial cells (3). Studies in human malignant melanoma strongly suggest that MUC18 is critical to tumor progression, such as metastasis (30).…”

“…It is controversial whether MUC18 should be included in the mucin (i.e., cell membrane-tethered mucins) family because it lacks the typical tandem repeat structure of mucins. Human MUC18 is a type I transmembrane glycoprotein with 646 amino acids (molecular weight, 113 kD) (2,3). MUC18 aberrant overexpression was initially identified in human malignant melanoma cells, which may promote tumor metastasis (4)(5)(6).…”

CD146 expression on primary nonhematopoietic bone marrow stem cells is correlated with in situ localization

“…28 We also observed that in vitro CD146 expression was dependent on oxygen levels and that in situ CD146 expression near the bone surface was absent or very weak. These observations might partly be explained by lower oxygen levels at the endosteum; however, additional mechanisms such as calcium-induced CD146 shedding might be operative as well, 33 because calcium levels are high near activated osteoclasts at the endosteal surface. 34 In summary, we have defined the phenotype of human primary nonhematopoietic BM-MSCs based on the expression of CD271, CD45, and CD146.…”