Transforming growth factor-beta 1 lowers the CD14 content of monocytes.
Marked elevation of transforming growth factor-beta 1 (TGF-beta 1) has been demonstrated clinically following injury and in sepsis. While alterations in the monocyte binding site (CD14) for the lipopolysaccharide (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 leukocytes were isolated from healthy donors with discontinuous gradient centrifugation and incubated at 37 degrees C for 2 and 24 hr with increasing doses of purified human platelet TGF-beta 1. Monocytes were immunofluorescently 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). At 24 hr, there was no significant difference between cells stimulated by TGF-beta 1 and control cells. To confirm that TGF-beta 1 was active 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 physiologic 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 patients.
Hamon
G
G
Department of Surgery, San Francisco General Hospital, University of California 94143.
Mulloy
R H
RH
Chen
G
G
Chow
R
R
Birkenmaier
C
C
Horn
J K
JK
D015703:Antigens, CD / Q000378:metabolism*; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism*; D015415:Biomarkers; D015536:Down-Regulation; D005434:Flow Cytometry; D006801:Humans; D018950:Lipopolysaccharide Receptors; D009000:Monocytes / Q000378:metabolism*; D017452:Receptors, IgG / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015415:Biomarkers; D018950:Lipopolysaccharide Receptors; D017452:Receptors, IgG; D016212:Transforming Growth Factor beta