Selective deactivation of human monocyte functions by TGF-beta.
TGF-beta at 1 and 10 ng/ml inhibited H2O2 production and fibronectin adherence by human monocytes. Coculture with anti-TGF-beta Abs or with IFN-gamma, but not with growth hormone, abrogated these effects. Neither viability nor superoxide production were decreased by TGF-beta treatment. TGF-beta appeared to be inhibiting H2O2 production rather than inducing catalase as preincubation in azide was without effect. Also, TGF-beta did not inhibit activity against virulent Mycobacterium tuberculosis. Coculture of monocytes with IFN-gamma + TGF-beta in vitro moderately inhibited the growth of M. tuberculosis when compared with untreated cells. Phagocytosis was not inhibited. Treatment of monocytes with another combination of cytokines, IFN-gamma+ TNF-alpha + vitamin D3, markedly reduced bacterial viability, although this appeared to be due to decreased phagocytosis leading to extracellular death of the bacteria. We conclude that despite suppressing some monocyte functions such as H2O2 production and adherence, TGF-beta, in combination with other cytokines, leaves other antimicrobial functions of the monocyte unaffected or even enhanced.
Warwick-Davies
J
J
Host Defence Unit, National Heart and Lung Institute, Royal Brompton Hospital, London, United Kingdom.
Lowrie
D B
DB
Cole
P J
PJ
D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D005353:Fibronectins; D006801:Humans; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors*; D009000:Monocytes / Q000187:drug effects* / Q000382:microbiology / Q000502:physiology; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D010587:Phagocytosis; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D005353:Fibronectins; D016212:Transforming Growth Factor beta; D006861:Hydrogen Peroxide