HEMATOPOIETIC PLACENTAL PROTEIN-14 - AN IMMUNOSUPPRESSIVE FACTOR IN CELLS OF THE MEGAKARYOCYTIC LINEAGE

Placental protein 14 (PP14), an immunosuppressive molecule previously known to be expressed in the female and male reproductive tracts only, was shown to be expressed by hematopoietic cells of the megakaryocyti c lineage. Northern blot analysis confirmed the induction specificity of PP14 mRNA in phorbol ester-treated K562 cells. Potent immunosuppres sive activity in conditioned medium from phorbol ester-treated K562 ce lls was attributed to hematopoietic PP14 by anti-PP14 antibody blockin g. Immunoprecipitation with anti-PP14 antibodies front conditioned med ium revealed two distinct PP14 protein isoforms, designated PP14.1 and PP14.2. Polymerase chain reaction cloning and analysis demonstrated t he presence of distinct mRNA counterparts to PP14.1 and PP14.2 that ha d not been resolved by Northern blot analyses. Hematopoietic PP14.1 mR NA corresponds in size to endometrial PP14 mRNA, whereas the smaller h ematopoietic PP14.2 mRNA displays an internal in-frame 66-nucleotide d eletion that can be explained by alternative splicing and predicts a 2 2-amino-acid deletion ill the encoded gene product. Both PP14 mRNA iso forms were additionally detected by reverse transcriptase polymerase c hain reaction analyses in two human megakaryocytic cell lines and in n ormal human megakaryocytes and platelets. PP14 mRNA was not detected b y reverse transcriptase polymerase chain reaction in a panel of nonhem atopoietic, nonendometrial tissues examined. The finding of hematopoie tic PP14 within the megakaryocytic lineage provides an additional regu latory lint between the coagulation and immune systems in normal and p athological settings.