alpha 4 integrins mediate lymphocyte attachment and rolling under physiologic flow.
Of the several families of adhesion receptors involved in leukocyte-endothelial cell interactions, only the selectins have been shown to initiate leukocyte interaction under physiologic shear; indeed, beta 2 (CD18) intergrins responsible for neutrophil arrest are unable to engage without prior selectin-mediated rolling. In contrast, alpha 4 (CD49d) integrins are shown here to initiate lymphocyte contract ("tethering") in vitro under shear and in the absence of a selectin contribution. The alpha 4 integrin ligands MAdCAM-1 and VCAM-1 support loose reversible interactions including rolling, as well as rapid sticking and arrest that is favored following integrin activation. Moreover, alpha 4 beta 7 mediates L-selectin (CD62L)-independent attachment of blood-borne lymphocytes to lamina propria venules in situ. Scanning electron microscopy of alpha 4 beta 7hi lymphoid cells reveals that, like L-selectin, alpha 4 beta 7 is highly concentrated on microvillous sites of initial cellular contact, whereas the beta 2 integrin LFA-1 is excluded from villi. Thus, alpha 4 but not beta 2 integrins can initiate leukocyte adhesion under flow, a capacity that may be in part a function of topographic presentation on microvilli.
Berlin
C
C
Department of Pathology, Stanford University, California 94305.
Bargatze
R F
RF
Campbell
J J
JJ
von Andrian
U H
UH
Szabo
M C
MC
Hasslen
S R
SR
Nelson
R D
RD
Berg
E L
EL
Erlandsen
S L
SL
Butcher
E C
EC
D000818:Animals; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002450:Cell Communication; D002465:Cell Movement; D007136:Immunoglobulins / Q000378:metabolism; D039441:Integrin alpha4; D039641:Integrin beta Chains; D016023:Integrins / Q000032:analysis / Q000378:metabolism / Q000502:physiology*; D007421:Intestine, Small / Q000098:blood supply; D008213:Lymphocyte Activation; D016169:Lymphocyte Function-Associated Antigen-1 / Q000032:analysis; D008214:Lymphocytes / Q000166:cytology* / Q000648:ultrastructure; D051379:Mice; D008871:Microvilli / Q000737:chemistry; D009088:Mucoproteins / Q000378:metabolism; D014407:Tumor Cells, Cultured; D019010:Vascular Cell Adhesion Molecule-1; D014699:Venules / Q000378:metabolism
D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; D039641:Integrin beta Chains; D016023:Integrins; D016169:Lymphocyte Function-Associated Antigen-1; C489082:Madcam1 protein, mouse; D009088:Mucoproteins; D019010:Vascular Cell Adhesion Molecule-1; C091368:integrin beta7; D039441:Integrin alpha4