A central role for microvillous receptor presentation in leukocyte adhesion under flow.
Leukocyte adhesion to endothelium requires specialized mechanisms for contact initiation under flow. L-selectin (CD62L), an efficient initiator of adhesion, is clustered on the tips of leukocyte microvilli. To test whether microvillous presentation is critical for contact formation ("tethering"), we transfected lymphoid cells with chimeras of L-selectin and CD44, an adhesion molecule that is excluded from microvilli. CD44 transmembrane and intracellular (TM-IC) domains targeted the L-selectin ectodomain to the planar body, whereas L-selectin TM-IC segments conferred CD44 ectodomain clustering on microvilli. Wild-type and chimeric transfectants bound similarly to anti-ectodomain MAbs in static assays, but MAb binding under flow was much more efficient in the context of microvillous presentation. Similarly, wild-type and chimeric L-selectin possessed equivalent lectin activity, but microvillous presentation dramatically enhanced contact initiation on a native ligand. These findings demonstrate a critical role for receptor topography in leukocyte adhesion and suggest a novel regulatory mechanism of leukocyte trafficking.
von Andrian
U H
UH
Center for Blood Research, Harvard Medical School, Boston, Massachusetts 02115, USA.
Hasslen
S R
SR
Nelson
R D
RD
Erlandsen
S L
SL
Butcher
E C
EC
D000818:Animals; D001402:B-Lymphocytes / Q000648:ultrastructure*; D002448:Cell Adhesion / Q000276:immunology*; D004727:Endothelium / Q000166:cytology; D006801:Humans; D018960:Hyaluronan Receptors / Q000276:immunology / Q000378:metabolism; D019041:L-Selectin / Q000276:immunology; D016393:Lymphoma, B-Cell / Q000473:pathology / Q000648:ultrastructure; D051379:Mice; D016253:Microscopy, Immunoelectron; D008871:Microvilli / Q000276:immunology / Q000648:ultrastructure*; D011485:Protein Binding / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000276:immunology; D012212:Rheology; D014162:Transfection / Q000276:immunology; D014407:Tumor Cells, Cultured / Q000276:immunology / Q000378:metabolism
D018960:Hyaluronan Receptors; D011993:Recombinant Fusion Proteins; D019041:L-Selectin