Interleukin-2 and interferon-gamma recruit different subsets of human peripheral blood monocytes to secrete interleukin-1 beta and tumour necrosis factor-alpha.
Exposure of cultured human peripheral blood monocytes (PBMO) to interferon-gamma (IFN-gamma) enhances surface expression of the p55 subunit of the interleukin-2 receptor (IL-2R). Addition of IL-2 to IFN-gamma treated monocytes will stimulate subsequent release of interleukin-1 beta (IL-1 beta) and tumour necrosis factor-alpha (TNF-alpha) due to enhancement of the transcriptional rate and stability of mRNA accumulation of both genes. The present study was aimed to investigate whether IFN-gamma and IL-2 will favour the release of IL-1 beta and TNF-alpha by different subsets of human PBMO. To this end PBMO were separated into four fractions with densities ranging from 1.058 to 1.075 kg/l by means of discontinuous bovine serum albumin (BSA) gradient centrigugation. Following incubation of monocyte subsets in the presence or absence of IFN-gamma and IL-2 for a culture period of 24-48 h, cell-free culture supernatants were collected and assayed for IL-1 beta and TNF-alpha activity by ELISA. Surface p55 IL-2R expression was detected by CD25 monoclonal antibody (MoAb) anti-IL-2R1 using immunofluorescence analysis. Although IL-2R1 expressing PBMO were equally distributed among the four fractions, IL-1 beta secretion was found to reside mainly in the most dense fraction. The major TNF-alpha activity was detected, however, in supernatants obtained from cultures of PBMO with densities of 1.065-1.075 kg/l. These data demonstrate functional heterogeneity of subsets of human PBMO with respect to their capacity to produce distinct cytokines.
Herrmann
F
F
Department of Haematology, Johannes Gutenberg-University of Mainz, FRG.
Gebauer
G
G
Lindemann
A
A
Brach
M
M
Mertelsmann
R
R
D002478:Cells, Cultured; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D007375:Interleukin-1 / Q000502:physiology*; D007376:Interleukin-2 / Q000494:pharmacology*; D009000:Monocytes / Q000145:classification / Q000378:metabolism*; D015375:Receptors, Interleukin-2 / Q000032:analysis; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D007375:Interleukin-1; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma