C3 molecules internalize and enhance the growth of Lewis lung carcinoma cells

C3 molecules from normal murine serum are mainly bound to Lewis lung carcin oma cells (3LL) that do not express CRs, mainly through covalent binding as determined by the appearance of bands stained with anti-C3 and larger than 190 kD in immunoblots of proteins in whole cell extracts. Methylamine-trea ted, or zymosan-treated normal mouse serum, heat inactivated, or EDTA-treat ed murine serum resulted in low C3 deposition on 3LL cells, as indicated by fluorescence tests and immunoblotting. Cytofluorimetric studies showed tha t C3 molecules bound to 3LL cells were internalized in a time- and temperat ure-dependent process. This was confirmed by electronmicroscopic studies. T he conditions allowing C3 fixation to acceptor sites and subsequent interna lization increased cell proliferation. This was also true, when serum from mice genetically deficient in C5 was used which stresses the role of C3 in contrast to effects of membrane attack complex formation.