Rapid cytokine up-regulation of integrins, complement receptor 1 and HLA-DR on monocytes but not on lymphocytes.
Short-term (3 hr) incubation of whole blood with human recombinant cytokines induced rapid changes in the expression of monocyte but not of lymphocyte surface molecules. The percentage of monocytes bearing CD11b molecules was enhanced by tumour necrosis factor-beta (TNF-beta), whilst that of CD11c was increased by both TNF-alpha and TNF-beta. The mean fluorescence intensity (MFI) of monocyte CD11a was enhanced by interleukin-2 (IL-2), TNF-alpha and TNF-beta, and that of CD11b, CD11c and CD18 was increased by IL-2, IL-4, TNF-alpha and TNF-beta. The proportion of monocytes expressing HLA-DR antigens was not modified by the cytokines investigated, but its MFI was increased by IL-2, IL-4, TNF-alpha and TNF-beta. In contrast, the percentage of monocytes bearing complement receptor 1 (CD35) was enhanced by IL-2, TNF-alpha and TNF-beta but the MFI of this molecule was not modified by these cytokines. The highest up-regulation of CD18, HLA-DR and CD35 was observed with 100 U/ml of either IL-2, IL-4, TNF-alpha or TNF-beta. Decreasing the concentration of all four cytokines from 100 to 10 and 1 U/ml diminished the levels of expression of all molecules, with the exception of CD35, which reached its maximum upon incubation with 1 U/ml of TNF-alpha. IL-1 beta, IL-6 or interferon-gamma (IFN-gamma) did not modify the expression of any of the above monocyte surface determinants. Moreover, none of the lymphocyte surface molecules investigated was modified by 3-hr incubation of blood with cytokines. The demonstration that cytokines selectively and rapidly up-regulate integrins, complement receptor 1 and HLA-DR molecules, on monocytes but not on lymphocytes, suggests that similar mechanisms of mononuclear cell activation by cytokines may control the development and duration of the inflammatory process.
Immunology Research Unit, Rayne Institute, St Thomas' Hospital, London, U.K.
G A
GA
Limb
A S
AS
Hamblin
R A
RA
Wolstencroft
D C
DC
Dumonde
D015703:Antigens, CD / Q000032:analysis; D018845:CD11 Antigens; D018821:CD18 Antigens; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D006684:HLA-DR Antigens / Q000032:analysis*; D006801:Humans; D016023:Integrins / Q000032:analysis*; D008214:Lymphocytes / Q000276:immunology; D009000:Monocytes / Q000276:immunology*; D017463:Receptors, Complement 3b / Q000032:analysis*; D011994:Recombinant Proteins / Q000276:immunology
D015703:Antigens, CD; D018845:CD11 Antigens; D018821:CD18 Antigens; D016207:Cytokines; D006684:HLA-DR Antigens; D016023:Integrins; D017463:Receptors, Complement 3b; D011994:Recombinant Proteins