Hyaluronan-independent adhesion of CD44H+ and CD44v10+ lymphocytes to dermal microvascular endothelial cells and keratinocytes.
We have recently shown the CD44 variant isoform 10 (CD44v10) to be expressed on reactive as well as malignant cutaneous lymphocytes; however, the functional consequences of CD44v10 expression on lymphocytes are not elucidated. By using appropriately transfected lymphatic cells we analyzed the role of CD44v10 on lymphocytes in cell-matrix adhesion and homotypic and heterotypic cell-cell adhesion assays. Despite a low binding affinity to hyaluronan, CD44v10-expressing lymphocytes exhibited heterotypic cell-cell adhesion to inflamed dermal microvascular endothelium and keratinocytes, as indicated by Stamper-Woodruff assays on tissue sections of delayed type hypersensitivity reactions and adhesion assays with cultured keratinocytes and cytokine-stimulated human dermal microvascular endothelial cells. Antibody-blocking assays excluded interaction of CD44v10 with the principal CD44 ligand hyaluronan as well as involvement of selectins or integrins in these heterotypic cell-cell adhesion assays. In contrast, cellular aggregation assays with fluorescence-labeled CD44v10- and CD44H-expressing lymphocytes revealed homotypic CD44v10/CD44v10 binding as well as binding of CD44v10 with CD44H. Heterotypic cell-cell adhesion assays with ultraviolet-A-irradiated CD44v-negative cytokine-stimulated endothelial cells demonstrated binding kinetics of CD44v10-expressing lymphocytes paralleling those of endothelial CD44H expression. These results imply that a hyaluronan-independent CD44v10/CD44H-mediated pathway is involved in lymphocyte infiltration into the dermis and epidermis of inflamed skin and suggest modulation of CD44H expression on inflamed dermal microvascular endothelium as a mechanism of ultraviolet-A-induced therapeutic effects on the skin.
Weimann
T K
TK
Department of Dermatology, University of Essen, Germany.
Wagner
C
C
Funk
R
R
Hirche
H
H
Goos
M
M
Wagner
S N
SN
D002448:Cell Adhesion; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology*; D005091:Exons; D014644:Genetic Variation; D006801:Humans; D018960:Hyaluronan Receptors / Q000032:analysis* / Q000378:metabolism / Q000502:physiology; D006820:Hyaluronic Acid / Q000378:metabolism / Q000502:physiology*; D016023:Integrins / Q000502:physiology; D015603:Keratinocytes / Q000502:physiology*; D008214:Lymphocytes / Q000502:physiology*; D008833:Microcirculation; D019087:Selectins / Q000502:physiology; D012867:Skin / Q000098:blood supply*
C117722:CD44v10 antigen; D018960:Hyaluronan Receptors; D016023:Integrins; D019087:Selectins; D006820:Hyaluronic Acid