title: Leukocyte adhesion molecule-1 (LAM-1, L-selectin) interacts with an inducible endothelial cell ligand to support leukocyte adhesion.
abstract: The human lymphocyte homing receptor, LAM-1, mediates the adhesion of lymphocytes to specialized high endothelial venules (HEV) of peripheral lymph nodes. We now report that LAM-1 is also a major mediator of leukocyte attachment to activated human endothelium. In a novel adhesion assay, LAM-1 was shown to mediate approximately 50% of the adhesion of both lymphocytes and neutrophils to TNF-activated human umbilical vein endothelial cells at 4 degrees C. The contribution of LAM-1 to leukocyte adhesion was only detectable when the assays were carried out under rotating (nonstatic) conditions, suggesting that LAM-1 is involved in the initial attachment of leukocytes to endothelium. In this assay at 37 degrees C, essentially all lymphocyte attachment to endothelium was mediated by LAM-1, VLA-4/VCAM-1, and the CD11/CD18 complex, whereas neutrophil attachment was mediated by LAM-1, endothelial-leukocyte adhesion molecule-1, and CD11/CD18. Thus, multiple receptors are necessary to promote optimal leukocyte adhesion to endothelium. LAM-1 also appeared to be involved in optimal neutrophil transendothelial migration using a videomicroscopic in vitro transmigration model system. LAM-1-dependent leukocyte adhesion required the induction and surface expression of a neuraminidase-sensitive molecule that was expressed for at least 24 h on activated endothelium. Expression of the LAM-1 ligand by endothelium was optimally induced by LPS and the proinflammatory cytokines TNF-alpha and IL-1 beta, whereas IFN-gamma and IL-4 induced lower levels of expression. The LAM-1 ligand on HEV and cytokine treated endothelium may be similar carbohydrate-containing molecules, because phosphomannan monoester core complex from yeast Hansenula hostii cell wall blocked binding of lymphocytes to both cell types, and identical epitopes on LAM-1-mediated lymphocyte attachment to HEV and activated endothelium. Thus, LAM-1 and its inducible endothelial ligand constitute a new pair of adhesion molecules that may regulate initial leukocyte/endothelial interactions at sites of inflammation.
authors.affiliation: Division of Tumor Immunology, Dana-Farber Cancer Institute, Boston, MA 02115-6084.
authors.forename: O
authors.initials: O
authors.lastname: Spertini
authors.forename: F W
authors.initials: FW
authors.lastname: Luscinskas
authors.forename: G S
authors.initials: GS
authors.lastname: Kansas
authors.forename: J M
authors.initials: JM
authors.lastname: Munro
authors.forename: J D
authors.initials: JD
authors.lastname: Griffin
authors.forename: M A
authors.initials: MA
authors.lastname: Gimbrone
authors.forename: T F
authors.initials: TF
authors.lastname: Tedder
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD / Q000502:physiology; D018845:CD11 Antigens; D018821:CD18 Antigens; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000502:physiology*; D002465:Cell Movement; D016207:Cytokines / Q000494:pharmacology; D019040:E-Selectin; D004730:Endothelium, Vascular / Q000502:physiology*; D000939:Epitopes; D006801:Humans; D019041:L-Selectin; D007962:Leukocytes / Q000502:physiology*; D008024:Ligands; D019007:P-Selectin; D010980:Platelet Membrane Glycoproteins / Q000502:physiology*
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018845:CD11 Antigens; D018821:CD18 Antigens; D015815:Cell Adhesion Molecules; D016207:Cytokines; D019040:E-Selectin; D000939:Epitopes; D008024:Ligands; D019007:P-Selectin; D010980:Platelet Membrane Glycoproteins; D019041:L-Selectin