Tumor cytostasis mediated by a monoclonal IgM antibody promoting adhesion between macrophages and tumor cells. Evidence for a lectin-like behavior.
We have shown previously that an IgM mAb (A10) recognizing Ehrlich tumor (ET) cell surface carbohydrates, inhibits in vivo ET growth by a macrophage-dependent mechanism. The inhibition mechanism involving both IgM and macrophages was unclear because receptors for IgM on macrophages are controversial and another monoclonal IgM (E1), also recognizing ET cell surface carbohydrates, was completely unable to show any protective effect. Here we show that A10, but not E1, was able to promote adhesion between macrophages and ET cells by a receptor for IgM-independent mechanism. Immunofluorescence studies showed that A10, but not E1, did react with macrophages if these cells were preincubated with a source of Ag spontaneously released from ET cells. This Ag release appeared to be required for A10-mediated adhesion, because adhesion was not obtained when ET cells fixed with paraformaldehyde were used. Cytostasis studies performed with macrophages stimulated with L-929 conditioned medium and ET cells showed that A10, but not E1 nor unrelated IgM, was able to inhibit ET cell proliferation in vitro by a mechanism involving cell contact between both cell populations. Therefore, IgM inhibition of ET growth, both in vivo and in vitro, could be explained by a lectin-like mechanism, where IgM, recognizing Ag of tumor origin, bridges macrophages to tumor cells.
Subiza
J L
JL
Department of Immunology, Hospital Universitario San Carlos, Madrid, Spain.
Gil
J
J
Rodríguez
R
R
Ruiz de Morales
J G
JG
Viñuela
J E
JE
de la Concha
E G
EG
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D002448:Cell Adhesion; D002450:Cell Communication; D003602:Cytotoxicity, Immunologic; D005260:Female; D007075:Immunoglobulin M / Q000276:immunology*; D037102:Lectins / Q000502:physiology*; D008264:Macrophages / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000473:pathology*
D000911:Antibodies, Monoclonal; D007075:Immunoglobulin M; D037102:Lectins