TRANSFORMING GROWTH FACTOR-BETA(1) LOWERS THE CD14 CONTENT OF MONOCYTES

Marked elevation of transforming growth factor-beta(1) (TGF-beta(1)) h as been demonstrated clinically following injury and in sepsis. While alterations in the monocyte binding site (CD14) for the lipopolysaccha ride (LPS)-lipopolysaccharide binding protein (LBP) complex have been noted with exposure to LPS, immune complexes, gamma-interferon, and IL -4, it is not known whether TGF-beta(1) can alter CD14 expression. To study the effect of TGF-beta(1) on monocyte CD14 expression, human leu kocytes were isolated from healthy donors with discontinuous gradient centrifugation and incubated at 37 degrees C for 2 and 24 hr with incr easing doses of purified human platelet TGF-beta(1). Monocytes were im munofluorescently stained with monoclonal antibodies recognizing CD14 and CD16. The cells were analyzed by flow cytometry. At 2 hr, 50 ng/ml TGF-beta(1) significantly lowered CD14 expression (51%, P = 0.043). A t 24 hr, there was no significant difference between cells stimulated by TGF-beta(1) and control cells. To confirm that TGF-beta(1) was acti ve at 24 hr, we examined levels of CD16. CD16 expression was increased by 10 ng/ml of TGF-beta(1). These observations suggest that high phys iologic concentrations of TGF-beta(1) cause early monocyte suppression of CD14. Thus, CD14 may be marker for the transition of monocytes to macrophages and TGF-beta(1) may be responsible for the down-regulation of CD14 expression observed in monocytes obtained from septic patient s. (C) 1994 Academic Press, Inc.