Dual Role of Melanoma Cell Adhesion Molecule (MCAM)/CD146 in Lymphocyte Endothelium Interaction: MCAM/CD146 Promotes Rolling via Microvilli Induction in Lymphocyte and Is an Endothelial Adhesion Receptor

Abstract

The melanoma cell adhesion molecule (MCAM)/CD146 is expressed as two isoforms differing by their cytoplasmic domain (MCAM long (MCAM-l) and MCAM short (MCAM-s)). MCAM being expressed by endothelial cells and activated T cells, we analyzed its involvement in lymphocyte trafficking. The NK cell line NKL1 was transfected by MCAM isoforms and submitted to adhesion on both the endothelial cell monolayer and recombinant molecules under shear stress. MCAM-l transfection reduced rolling velocity and increased NKL1 adhesion on the endothelial cell monolayer and VCAM-1. Scanning electron microscopy revealed that MCAM-l induced microvilli formation and extension. In contrast, MCAM short or mock transfection had no effect on adhesion of NKL1 cells and microvilli formation. As shown by mutagenesis, serine 32 of the MCAM-l cytoplasmic tail, belonging to a putative protein kinase C phosphorylation site, was necessary for MCAM-l-actin cytoskeleton interaction and microvilli induction. Accordingly, chelerythrine chloride, a protein kinase C inhibitor, abolished MCAM-l-induced microvilli and rolling of MCAM-l-transfected NKL1 cells. Inhibition of adhesion under shear stress by anti-MCAM Abs suggested that both lymphoid MCAM-l and endothelial MCAM were also directly involved in lymphocyte endothelium interaction. MCAM-l-transfected NKL1 and activated CD4 T cells adhered to rMCAM under shear stress whereas anti-MCAM Ab treatment inhibited this process. Taken together, these data establish that MCAM is involved in the initial steps of lymphocyte endothelium interaction. By promoting the rolling on the inflammation marker VCAM-1 via microvilli induction and displaying adhesion receptor activity involving possible homophilic MCAM-l-MCAM-l interactions, MCAM might be involved in the recruitment of activated T cells to inflammation sites.

Mouse CD146/MCAM is a marker of natural killer cell maturation

“…The levels of CD146 transcripts were measured by quantitative RT-PCR. Two isoforms of CD146 were previously reported in human endothelial cells and Guezguez et al have reported that the ectopic expression of each isoform in the CD146-negative NKL1 human NK cell line confers to these cells distinct adhesive properties to endothelial cells [23,24]. We found that both isoforms are expressed by the three subsets of NK cells and the transcript levels correlated with those of CD146 protein detected in these subsets (Fig.…”

Expansion of human NK-22 cells with IL-7, IL-2, and IL-1β reveals intrinsic functional plasticity

“…1D). Many of these molecules have been shown to mediate adhesion (14,15). Cells cultured in IL-2 plus IL-7 expressed more NKG2D and CD94 than cells cultured in IL-7 alone (Fig.…”

Expression of the melanoma cell adhesion molecule in human mesenchymal stromal cells regulates proliferation, differentiation, and maintenance of hematopoietic stem and progenitor cells

“…11 MCAM function has been extensively studied in melanomas and other types of cancer (prostate cancer and breast cancer), but the ligand for MCAM has not yet been identified. [12][13][14] This study aimed to clarify the impact of MCAM expression on the functional properties of hMSC and the maintenance of HSPC in co-culture. Thus, we generated primary hMSC that stably expressed shRNA against MCAM or that over-expressed an MCAM coding sequence (CDS) through lentiviral vector gene transfer.…”