C1Q RECEPTORS - REGULATING SPECIFIC FUNCTIONS OF PHAGOCYTIC-CELLS

A C1q receptor that upregulates the phagocytic capacity of professiona l phagocytes, C1qR(p), has been identified, and its primary structure determined by cDNA cloning and sequencing. Monoclonal antibodies that immunoprecipitate this 126,000 Mr polypeptide inhibit the enhancement of phagocytosis triggered not only by C1q but also by mannose binding lectin (MBL) and pulmonary surfactant protein A (SPA) providing critic al evidence that this polypeptide is a functional receptor or componen t of the receptor that mediates this enhancement of phagocytosis. The amino acid sequence, deduced from the cloned cDNA coding for this rece ptor, indicates that this surface glycoprotein receptor is a novel typ e I membrane protein of 631 amino acid containing a region homologous to C-type lectin carbohydrate recognition domains, 5 EGF-like domains, a single transmembrane domain and a 47 amino acid intracellular domai n. Expression of this receptor is limited to cells of myeloid origin, platelets and endothelial cells, consistent with a relatively selectiv e function, and making it an attractive candidate for therapeutic modu lation of function. A distinct C1q receptor that triggers superoxide i n polymorphonuclear leukocytes has been functionally characterized and designated as C1qR(O2-). Thus, the accumulated data that will be summ arized here demonstrate that there are at least two C1q receptor/recep tor complexes (C1qR(p) and C1qR(O2-)), each triggering distinct cellul ar responses, that multiple C1q receptors can be expressed on the same , as well as on different, cell types, and that at least one C1q recep tor, C1qR(p), is capable of responding to multiple ligands.