L1 ADHESION MOLECULE ON HUMAN-LYMPHOCYTES AND MONOCYTES - EXPRESSION AND INVOLVEMENT IN BINDING TO ALPHA-V-BETA-3 INTEGRIN

The L1 adhesion molecule is a member of the immunoglobulin (Ig) superf amily initially identified in the nervous system which contains six Ig -Iike domains. Besides the known L1-L1 homotypic interaction, L1 was r ecently shown to bind to very late antigen (VLA)-5 in the mouse and al pha v beta 3 in the human. The sixth Ig domain is critical for this fu nction, We now demonstrate that human CD4(+) peripheral blood T lympho cytes, monocytes and B lymphocytes, but not CD8(+) Tlymphocytes, expre ss LI. When compared to the expression of CD31, another ligand for alp ha v beta 3 on T lymphocytes, only a small proportion of cells were CD 31(+)L1(+) double positive. L1 was also detected on the surface of hum an monocytic and lymphoid turner lines and was shown to have a molecul ar mass of similar to 220 kDa, similar to the molecule present on neur oblastoma cells. The function of the sixth Ig domain of human LI as an integrin ligand was also investig ated. Using an RGD-containing pepti de derived from the sixth Ig domain as well as a fusion protein of the sixth Ig domain of L1 and the Fe Portion of human IgG1 (fi,LI-Fc), we demonstrated the binding of human MED-B1 (alpha v beta 3(In), alpha 5 beta 1(lo)) tumor cells and this binding was blocked by alpha v-speci fic mAb. In contrast, human Nalm-6 cells (alpha v beta(lo), alpha 5 be ta 1(hi)) did not bind to the 6.L1-Fe fusion protein. MED-BI cells cou ld also be stained with the 6.L1-Fc fusion protein. Our results sugges t that human L1 binds predominantly to alpha v beta 3 and that its pre sence on leukocytes could be important for adhesion and migration.