Factor B, the complement alternative pathway serine proteinase, is a major constitutive protein synthesized and secreted by resident and elicited mouse macrophages.
Factor B, the complement alternative pathway serine proteinase, a class III gene product of the major histocompatibility complex, is a major constitutive secretion product of mouse mononuclear phagocytes. This glycoprotein was synthesized and secreted by macrophages as a doublet of Mr 90,000 and 93,000 polypeptides that were immunoprecipitable with antibodies raised to human serum factor B, and that were indistinguishable from plasma factor B by immunoreactivity, peptide mapping, and molecular weight. Macrophage factor B was cleaved and activated to factor Bb- and Ba-like fragments by factor D and cobra venom factor. Some conversion of macrophage factor B to Bb-sized fragments occurred spontaneously in the conditioned culture medium after several hours. Factor B represented approximately 0.5% of newly synthesized protein and 4-6% of the secreted protein of resident peritoneal macrophages and macrophages elicited with thioglycollate broth, pyran copolymer, NaIO4, bacillus Calmette-Guerin, or Corynebacterium parvum. We detected synthesis of factor B immediately upon explanting these macrophages in culture; synthesis continued for several days in culture. The rate of secretion of factor B, as a proportion of total protein secretion in culture, remained constant with time. By radioimmunoassay, factor B antigens accumulated in the 24-h macrophage-conditioned culture medium at 2-10 nM, and was present in cell lysates at 4-8 nmol per 10(6) cells. We detected synthesis of factor B in bone marrow-derived macrophages as early as 5 d of culture. The P388D1 macrophage line synthesized factor B, but mouse L cells did not. In contrast, apolipoprotein E, another secreted protein of macrophages, was secreted by resident and thioglycollate-elicited macrophages but not by freshly harvested pyran copolymer-activated macrophages. Its synthesis was initiated at day 9 in culture of bone marrow-derived macrophages. These data support the classification of factor B as a constitutive biosynthetic and secreted protein of immature and mature macrophages in various states of activation. Production of factor B was modulated by treatment of macrophages in vivo or in culture with bacterial lipopolysaccharide endotoxin, which increased the synthesis, secretion, and accumulation of factor B up to 11-fold.
D000818:Animals; D001057:Apolipoproteins E / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D011415:Complement Factor B / Q000096:biosynthesis* / Q000302:isolation & purification; D004306:Dose-Response Relationship, Immunologic; D004792:Enzyme Precursors / Q000096:biosynthesis*; D005353:Fibronectins / Q000096:biosynthesis; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000145:classification / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008813:Mice, Inbred ICR; D008970:Molecular Weight; D010529:Peritoneal Cavity / Q000166:cytology; D010641:Phenotype
D001057:Apolipoproteins E; D004792:Enzyme Precursors; D005353:Fibronectins; D008070:Lipopolysaccharides; D011415:Complement Factor B