IDENTIFICATION OF FC-ALPHA RECEPTOR (CD89) ISOFORMS GENERATED BY ALTERNATIVE SPLICING THAT ARE DIFFERENTIALLY EXPRESSED BETWEEN FLOOD MONOCYTES AND ALVEOLAR MACROPHAGES

One of the hallmarks of mucosal-host defense is the clearance of inhal ed Ags by alveolar macrophages (AM) through interactions of IgA Abs an d IgA Fc receptors (Fc alpha R). AM constitutively expressed Fc alpha R at lower levels than freshly isolated and in vitro-differentiated mo nocytes as determined by immunofluorescence using four anti-fc alpha R mAb. SDS-PACE analysis of iodinated cell surface proteins revealed th at Fc alpha R on AM has an M(r) of 50 to 65 kDa, slightly lower than t hat on monocytes (55-75 kDa). Treatment of AM Fc alpha R by N-glycanas e gave rise to a protein core of 28 kDa, smaller than the 32-kDa backb one of blood monocytes. AM fc alpha R molecules were unaffected by pho sphatidylinositol-phospholipase C treatment. Fc alpha B transcripts we re analyzed by reverse transcription-PCR using primers in the 5' and 3 ' regions of a U937 Fc alpha R cDNA. Three transcripts were amplified, cloned, and sequenced from AM and/or monocyte mRNA, the full length F c alpha R and two alternatively spliced products corresponding to dele tions of 66 and 288 nucleotides in the portion coding for the extracel lular domain; they were named Fc alpha R a.1, a.2, and a.3, respective ly. These PCR products were transcribed and translated in vitro into t hree proteins (M(r) 32, 30, and 22 kDa, respectively), in which the 32 - and 30-kDa species were immunoprecipitated by an anti-Fc alpha R mAb . The predicted size of the protein encoded by the Fc alpha R a.2 tran script without the leader peptide is M(r) similar to 27,400, a value t hat is consistent with the M(r) of AM Fc alpha R backbone. These resul ts indicate that AM express at their surfaces a protein product of an alternatively spliced Fc alpha R transcript, the Fc alpha R a.2 isofor m, that might have physiologic relevance in IgA-mediated host defense at mucosal sites.