OXIDIZED LIPOPROTEIN(A) INDUCES CELL-ADHESION MOLECULE MAC-1 (CD-11B)AND ENHANCES ADHESION OF THE MONOCYTIC CELL-LINE U937 TO CULTURED ENDOTHELIAL-CELLS

Because of structural similarities between low density lipoproteins (L DL) and lipoprotein (a) (Lp(a)), we have investigated the properties a nd the functional activities of oxidized Lp(a) and focused on whether oxidized Lp(a), like oxidized LDL, can induce monocyte differentiation and adhesion of monocytic cells to endothelial cells grown in culture . Oxidized Lp(a), prepared in vitro by cupric ion oxidation, gave abso rption curves of conjugated dienes with a lag-phase of 61.7 +/- 6.6 mi n (mean +/- S.D.) as compared to 85.2 +/- 7.2 min (n = 6, P < 0.01) fo r oxidized LDL from the same donors and at equimolar concentrations. D egradation of oxidized I-125 Lp(a) by the monocytic cell line U937 at 37 degrees C was 1.6 +/- 0.3 nmol/g of cell protein, significantly (P < 0.01) greater than the degradation of oxidized I-125-LDL, which was 1.15 +/- 0.2 nmol/g of cell protein. Equimolar concentrations of oxidi zed Lp(a) and LDL inhibited the growth of U937 by 82 +/- 8.2% and 64 /- 7.1%, respectively, when compared with the effect (negligible) prod uced by native Lp(a) and LDL. In addition, equimolar concentrations of oxidized Lp(a) and LDL induced adhesion molecule, Mac-1 (CD 11b), exp ression in U937 by 64 +/- 7.1% and 58 +/- 6.1% (P > 0.05), respectivel y, of the effect produced by phorbol esters (PMA) (P < 0.01). U937 cel ls incubated with oxidized Lp(a) and LDL, showed an adherence to cultu red endothelial cells at 42 +/- 5.2% and 34 +/- 4.8%, respectively (P < 0.05), of the adherence shown by the same cells activated by PMA (P < 0.01). Our results suggest that oxidized Lp(a) like oxidized LDL pla ys an important role in the development of atherogenesis by inducing a dhesion of monocytes to the arterial intimal and by stimulating intima l monocytes to differentiate into macrophages.