LYSOSOME-ASSOCIATED MEMBRANE-PROTEINS H-LAMP1 (CD107A) AND H-LAMP2 (CD107B) ARE ACTIVATION-DEPENDENT CELL-SURFACE GLYCOPROTEINS IN HUMAN PERIPHERAL-BLOOD MONONUCLEAR-CELLS WHICH MEDIATE CELL-ADHESION TO VASCULAR ENDOTHELIUM

Lysosome-associated membrane proteins (LAMPs) are transmembrane lysoso mal glycoproteins which are detectable at the cell surface of lymphocy tes in patients with scleroderma and systemic lupus erythematosus. Whi le these proteins have been shown to mediate adhesion of tumor cells t o vascular endothelial selectins, the function of LAMPs expressed at t he cell surface of peripheral blood lymphocytes has not been previousl y examined. In the present study, the role of lamp2 (CD107b) in lympho cyte adhesion to vascular endothelium and the factors which influence in vitro cell surface expression of both lamp1 (CD107a) and lamp2 (CD1 07b) are examined. Freshly isolated PBMCs and unstimulated PBMCs in th e culture had low levels of cell surface lamp1 and lamp2 expression wh ich were significantly increased following PHA stimulation (P < 0.0001 ). A dose-dependent response to PHA and the effect of varying concentr ations of serum were defined. Kinetic analysis revealed that the major ity of the increase in both lamp1 and lamp2 occurred within the first 2 hr of incubation and that a subset of PBMCs maintained expression fo r at least 96 hr. Incubation of cells with colchicine and cycloheximid e modified the cell surface expression of these proteins. Interleukins 2, 4, 6, and 8 had only a modest effect on the degree of cell surface lamp1 and lamp2 expression, though they did significantly affect the distribution of expression among different subtypes of lymphoid cells. Under the conditions utilized in this study, cell surface LAMP expres sion was confined primarily to CD56(+) cells and to CD3(+) cells. Func tional analysis utilizing a fluorescence-based adhesion assay revealed that cell surface lamp2 mediates adhesion of PBMCs to vascular endoth elium, possibly by interacting with endothelial selectins. LAMPs likel y contribute to the migration of activated leukocytes to sites of infl ammation in vivo. (C) 1996 Academic Press, Inc.