Molecular cloning of a soluble form of the granulocyte-macrophage colony-stimulating factor receptor alpha chain from a myelomonocytic cell line. Expression, biologic activity, and preliminary analysis of transcript distribution.

Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104.

OBJECTIVE. To analyze the molecular and functional characteristics of a soluble form of the granulocyte-macrophage colony-stimulating factor receptor alpha chain (sGM-CSFR alpha), and analyze transcript expression in immune cells and the cellular constituents of rheumatoid arthritis synovial tissue. METHODS. We amplified, cloned, and expressed the sGM-CSFR alpha and transmembrane form of the receptor (tmGM-CSFR alpha) from complementary DNA derived from a human myelomonocytic cell line. Competitive polymerase chain reaction assays were developed to determine the absolute and relative amounts of tmGM-CSFR alpha versus sGM-CSFR alpha message synthesized by various cell lines and tissues. RESULTS. sGM-CSFR alpha transcripts were detected in bone marrow, monocyte/macrophages (cultured in GM-CSF), rheumatoid synovial tissue, and rheumatoid synovial tissue T cell lines, and represented the predominant transcript in synovial fibroblasts and osteoarthritis synovial tissue. Levels of expression in monocyte/macrophages and some synovial fibroblast and T cell lines approached those seen in transfected cell lines producing functional sGM-CSFR alpha. CONCLUSION. sGM-CSFR alpha represents a functional antagonist of GM-CSF activity in vitro. Expression of sGM-CSFR alpha in bone marrow, rheumatoid synovial tissue T cells, and synovial fibroblasts suggests an important role in vivo, both in regulating myelopoiesis and in modulating the immune response.

PMID: 7945472 [PubMed - indexed for MEDLINE]