Immature mast cells exhibit rolling and adhesion to endothelial cells and subsequent diapedesis triggered by E- and P-selectin, VCAM-1 and PECAM-1.
Mast cell numbers are markedly increased at sites of chronic inflammation. However, the underlying mechanisms of mast cell accumulation including mast cell progenitor trafficking remain to be identified in detail. Thus, the aim of this study was to identify the adhesion molecules involved in rolling, firm adhesion and transendothelial diapedesis of murine bone marrow-derived cultured mast cells (BMCMC) as a model for immature mast cells. We could show that BMCMCs exhibit in vivo rolling on skin vessel walls and strong adhesion to skin endothelial cells (ECs) in vitro under static and flow conditions. Interestingly, interaction of BMCMC with the EC adhesion molecules E- and P-selectin, vascular cell adhesion molecule-1 (VCAM-1) and platelet endothelial cell adhesion molecule-1 (PECAM-1) is required to mediate rolling and firm adhesion to ECs. The adhesion of BMCMCs to skin ECs is further enhanced by TNF, IL-4, IL-15 and vascular endothelial cell growth factor. Furthermore, BMCMCs exhibit directed and dose-dependent transmigration across an endothelial barrier, mediated by a PECAM-1-dependent mechanism. Our results demonstrate that BMCMCs can undergo a tightly regulated extravasation cascade consisting of rolling on and adhesion to endothelium and followed by directed diapedesis and reveal selectins, VCAM-1 and PECAM-1 as required adhesion molecules. These processes may contribute to mast cell accumulation in chronic inflammatory skin diseases and reveal opportunities to modulate peripheral tissue numbers of mast cells.
Dudeck
Anne
A
Department of Dermatology and Allergy, Allergie-Centrum-Charité, Charité-Universitätsmedizin Berlin, Germany. anne.dudeck@tu-dresden.de
Leist
Mandy
M
Rubant
Simone
S
Zimmermann
Anja
A
Dudeck
Jan
J
Boehncke
Wolf Henning
WH
Maurer
Marcus
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology*; D002461:Cell Line, Transformed; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D019040:E-Selectin / Q000276:immunology / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D039041:Integrin alpha4beta1 / Q000276:immunology / Q000378:metabolism; D039302:Integrin alphaVbeta3 / Q000276:immunology / Q000378:metabolism; D016023:Integrins / Q000276:immunology / Q000378:metabolism; D019409:Interleukin-15 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D008407:Mast Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D019007:P-Selectin / Q000276:immunology / Q000378:metabolism; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000276:immunology / Q000378:metabolism*; D019087:Selectins / Q000276:immunology / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D019010:Vascular Cell Adhesion Molecule-1 / Q000276:immunology / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D019040:E-Selectin; D039041:Integrin alpha4beta1; D039302:Integrin alphaVbeta3; D016023:Integrins; D019409:Interleukin-15; D008562:Membrane Glycoproteins; D019007:P-Selectin; C084882:P-selectin ligand protein; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D019087:Selectins; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D042461:Vascular Endothelial Growth Factor A; C071777:integrin alpha4beta7; D015847:Interleukin-4