Modulation of phenotypic and functional properties of human peripheral blood monocytes by IL-4.
Highly purified peripheral blood monocytes were cultured in the presence of rIL-4. Major changes in the morphology of the monocytes were observed. After day 5 of culturing the cells acquired a macrophage-like appearance, with increased cell size and extensive processes, suggesting that IL-4 may induce monocyte-macrophage differentiation. This notion is supported by the observed increased expression of MHC class II Ag, which is thought to be associated with monocyte differentiation. Exposure of monocytes to IL-4 resulted in a dose-dependent increase of the expression of MHC class II Ag, which became apparent after only 20 h of incubation. Maximal expression was obtained after incubation for 6 days, and persisted throughout the whole culture period. Similarly, IL-4 increased the expression of R for C3bi and p150.95 Ag, two members of the leukocyte function-associated Ag 1 family, whereas the expression of the third member, leukocyte function-associated Ag 1, remained unchanged during culture. Furthermore, it was shown that IL-4 inhibited the secretion of cytostatic and chemotactic compounds. Supernatants of monocytes cultured with IL-4 were, in contrast to control cultures, much less effective in inhibiting the growth of A375 melanoma cells. In addition, these supernatants failed to direct the migration of freshly isolated monocytes in a chemotaxis assay. Further analysis revealed that these supernatants exhibited reduced IL-1 activity, as measured in a mouse thymocyte proliferation assay, which might explain the low cytostatic and chemotactic activity. Taken together these results show that IL-4 modulates monocyte phenotype and function and may induce monocyte-macrophage differentiation in vitro.
te Velde
A A
AA
Division of Immunology, Netherlands Cancer Institute, Amsterdam.
Klomp
J P
JP
Yard
B A
BA
de Vries
J E
JE
Figdor
C G
CG
D000954:Antigens, Surface / Q000032:analysis; D002465:Cell Movement; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte; D003603:Cytotoxins / Q000096:biosynthesis; D006681:HLA-D Antigens / Q000032:analysis; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis; D015847:Interleukin-4; D007378:Interleukins / Q000494:pharmacology*; D016169:Lymphocyte Function-Associated Antigen-1; D009000:Monocytes / Q000145:classification* / Q000276:immunology / Q000378:metabolism; D010641:Phenotype
D000954:Antigens, Surface; D003603:Cytotoxins; D006681:HLA-D Antigens; D007375:Interleukin-1; D007378:Interleukins; D016169:Lymphocyte Function-Associated Antigen-1; D015847:Interleukin-4