title: Crosslinking of the human Fc receptor for IgA (FcalphaRI/CD89) triggers FcR gamma-chain-dependent shedding of soluble CD89.
abstract: CD89/FcalphaRI 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 receptor. We developed an ELISA for the detection of soluble CD89 (sCD89) forms and investigated the regulation of sCD89 production. PMA/ionomycin stimulation of monocytic cell lines (U937, THP-1, and MM6), but not of neutrophils, resulted in release of sCD89. Crosslinking of CD89 either via its ligand IgA or with anti-CD89 mAbs similarly resulted in sCD89 release. Using CD89-transfected cells, we showed ligand-induced shedding to be dependent on coexpression of the FcR gamma-chain subunit. Shedding of sCD89 was dependent on signaling via the gamma-chain and prevented by addition of inhibitors of protein kinase C (staurosporine) or protein tyrosine kinases (genistein). Western blotting revealed sCD89 to have an apparent molecular mass of 30 kDa and to bind IgA in a dose-dependent fashion. In conclusion, the present data document a ligand-binding soluble form of CD89 that is released upon activation of CD89-expressing cells. Shedding of CD89 may play a role in fine-tuning CD89 immune effector functions.
authors.affiliation: Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: G
authors.initials: G
authors.lastname: van Zandbergen
authors.forename: R
authors.initials: R
authors.lastname: Westerhuis
authors.forename: N K
authors.initials: NK
authors.lastname: Mohamad
authors.forename: J G
authors.initials: JG
authors.lastname: van De Winkel
authors.forename: M R
authors.initials: MR
authors.lastname: Daha
authors.forename: C
authors.initials: C
authors.lastname: van Kooten
mesh_terms: D015703:Antigens, CD / Q000276:immunology* / Q000302:isolation & purification / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005786:Gene Expression Regulation; D006023:Glycoproteins / Q000276:immunology* / Q000302:isolation & purification / Q000378:metabolism; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology* / Q000378:metabolism; D007152:Immunologic Capping; D009000:Monocytes / Q000276:immunology*; D009101:Multiple Myeloma / Q000097:blood; D011485:Protein Binding; D011961:Receptors, Fc / Q000276:immunology* / Q000302:isolation & purification / Q000378:metabolism; D012995:Solubility; D020298:U937 Cells
chemical_list: D015703:Antigens, CD; C036832:Fc(alpha) receptor; D006023:Glycoproteins; D007070:Immunoglobulin A; D011961:Receptors, Fc