Crosslinking of the human Fc receptor for IgA (Fc alpha RI/CD89) triggers FcR gamma-chain-dependent shedding of soluble CD89

CD89/Fc alpha RI is a 55- to 75-kDa type I receptor glycoprotein, expressed on myeloid cells, with important immune effector functions. At present, no information is available on the existence of soluble forms of this recepto r. We developed an ELISA fur the detection of soluble CD89 (sCD89) forms an d investigated the regulation of sCD89 production, PMA/ionomycin stimulatio n of monocytic cell lines (U937, THP-l,and MM6), but not of neutrophils, re sulted in release of sCDS9, Crosslinking of CD89 either via its ligand IgA or with anti-CD89 mAbs similarly resulted in sCD89 release. Using CD89-tran sfected cells, we showed ligand-induced shedding to be dependent on coexpre ssion of the FcR gamma-chain subunit, Shedding of sCD89 was dependent on si gnaling via the gamma-chain and prevented by addition of inhibitors of prot ein kinase C (staurosporine) or protein tyrosine kinases (genistein), Weste rn blotting revealed sCDS9 to have an apparent molecular mass of 30 kDa and to bind IgA in a dose-dependent fashion. In conclusion, the present data d ocument a ligand-binding soluble form of CD89 that is released upon activat ion of CD89-expressing cells, Shedding of CD89 may play a role in line-tuni ng CD89 immune effector functions.