Decreased production of TGF-beta 1 by human alveolar macrophages compared with blood monocytes.
As the main immunocytes lining pulmonary alveoli, alveolar macrophages (AM) are critical to the maintenance of immune hemostasis of the lung. This study examined the capacity of AM obtained from healthy individuals in comparison with autologous blood monocytes (MN) to produce transforming growth factor-beta 1 (TGF-beta), a pivotal molecule in regulation of immune responses and in promotion of fibrosis. AM produced negligible TGF-beta in response to LPS at both 24 and 72 h of culture. In contrast, LPS induced significant levels of TGF-beta in MN cultures (79.5 +/- 35 pg/ml in AM vs 890 +/- 162 pg/ml in MN, p less than 0.001, at 24 h). AM also produced significantly less TGF-beta than MN in response to phorbol ester and Con A. By northern blot analysis, constitutive expression of TGF-beta mRNA was lower in AM than MN at the time of isolation and after 24 h of culture. Lower expression of steady state TGF-beta message was not due to a more rapid decay of its mRNA in AM. Furthermore, TGF-beta mRNA expression was up-regulated by rTGF-beta in MN but was not induced in AM. In contrast to TGF-beta, LPS-stimulated AM produced sixfold higher levels of TGF-alpha at 24 h than MN (p less than 0.01). Production of IL-10 by LPS-stimulated AM was sixfold lower than MN (p less than 0.005) at 24 h of culture, but was comparable with MN at 72 h. Both 10-day cultured monocytes and peritoneal macrophages also had reduced capacity to produce TGF-beta. Therefore, the inability to produce TGF-beta may be a feature of more differentiated mononuclear phagocytes. In health, the reduced expression of TGF-beta by AM and the intact ability to produce TGF-alpha and IL-10 may favor a timely and regulated host response to inhaled pathogens while limiting potentially deleterious inflammatory responses.
Toossi
Z
Z
Department of Medicine, Case Western Reserve University, University Hospitals of Cleveland, OH 44106, USA.
Hirsch
C S
CS
Hamilton
B D
BD
Knuth
C K
CK
Friedlander
M A
MA
Rich
E A
EA
D002478:Cells, Cultured; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism*; D017737:Macrophages, Peritoneal / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D016212:Transforming Growth Factor beta / Q000096:biosynthesis* / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10