THE UROKINASE RECEPTOR (CD87) FACILITATES CD11B CD18-MEDIATED ADHESION OF HUMAN MONOCYTES/

Urokinase receptors (uPAR; CD87) form complexes with complement recept or 3 (CR3) (CD11b/CD18), a beta 2 integrin, In this study, we sought t o determine if this association modulates the adhesive function of CR3 . Both CR3 and uPAR concentrate at the ventral surface of fibrinogen-a dherent human monocytes, and CR3-uPAR coupling increases substantially upon adhesion to fibrinogen, Pretreatment with anti-uPAR monoclonal a ntibody reduced adhesion to CR3 counterligands (fibrinogen and keyhole limpet hemocyanin) by 50%, but did not affect adhesion to fibronectin , a beta 1 integrin counterligand, Antisense (AS) oligonucleotides wer e used to determine if selectively suppressing uPAR expression also mo dulates CR3 adhesive function, AS-uPAR oligo reduced CR3-dependent adh esion by 43 +/- 9% (P < 0.01), but did not affect CR3-independent adhe sion, To determine if the effects of uPAR are mediated through its lig and, monocytes were pre-treated with AS oligo to block uPA expression, Unlike the effects of blocking uPAR expression, AS-uPA oligo increase d adhesion by 46% (P < 0.005), and exogenous intact uPA, but not uPA f ragments, reversed this effect. We conclude that complex formation wit h uPAR facilitates the adhesive functions of CR3, This function of uPA R is not dependent upon its occupancy with uPA, which negatively influ ences adhesion.