Selective enhancement of Leu-CAM expression by interleukin 6 during differentiation of human promonocytic U937 cells.
Interleukin 6 (IL-6) is a cytokine with multiple biological activities on various tissues and cells. We have investigated the effect of recombinant human IL-6 (rhIL-6) on growth and differentiation of U937. Recombinant human IL-6 induced a dose-dependent growth inhibition, apparent around day 4, of up to 50% by day 8 of culture. Concomitant with this, changes in cytochemical activities were observed, indicative of differentiation. A panel of U937 antigens was analysed after culture with rhIL-6. Expression of the majority of these membrane antigens was unaffected, with the exception of two classes. First, rhIL-6 had a profound effect on members of the leucocytic cell adhesion molecules (Leu-CAM) family. Expression of the alpha-chain of CR3 (complement receptor 3; CD11b) was enhanced in a dose-dependent fashion, with maximal expression around day 7. Parallel to this a simultaneous increase in beta-chain (CD18) expression was found. Furthermore, enhanced expression of CR3 was, accompanied by increased rosetting with sheep erythrocytes sensitized with C3bi. A much lower, but significant, enhancement was observed for the alpha-chain of the p150,95 antigen (CD11c). Expression of leucocyte function-associated antigen-1, (LFA-1), (CD11a/CD18) remained unchanged. Remarkably, however, expression of a ligand of LFA-1, intercellular adhesion molecule-1 (ICAM-1; CD54), was enhanced with similar kinetics as CR3 and p150,95. A specific anti-rhIL-6 antiserum completely inhibited the IL-6 effect. These observations provide further support for an important role of IL-6 in the regulation of myeloid cell development in man.
Duits
A J
AJ
Department of Experimental Immunology, University Hospital Utrecht, The Netherlands.
Jainandunsing
S M
SM
van de Winkel
J G
JG
Capel
P J
PJ
D000911:Antibodies, Monoclonal / Q000276:immunology; D000954:Antigens, Surface / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000096:biosynthesis* / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line / Q000187:drug effects; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping; D015850:Interleukin-6 / Q000494:pharmacology*; D019041:L-Selectin; D009000:Monocytes / Q000276:immunology*; D011951:Receptors, Complement / Q000187:drug effects; D011994:Recombinant Proteins / Q000494:pharmacology; D012397:Rosette Formation
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D015815:Cell Adhesion Molecules; D015850:Interleukin-6; D011951:Receptors, Complement; D011994:Recombinant Proteins; D019041:L-Selectin