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 homeostasis of the lun g. This study examined the capacity of AM obtained from healthy indivi duals in comparison with autologous blood monocytes (MN) to produce tr ansforming growth factor-beta 1 (TGF-beta), a pivotal molecule in regu lation of immune responses and in promotion of fibrosis. AM produced n egligible 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 < 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 ex pression of TGF-beta mRNA was lower in AM than MN at the time of isola tion and after 24 h of culture. Lower expression of steady state TGF-b eta message was not due to a more rapid decay of its mRNA in AM. Furth ermore, TGF-beta mRNA expression was up-regulated by rTGF-beta in MN b ut was not induced in AM. In contrast to TGF-beta, LPS-stimulated AM p roduced sixfold higher levels of TGF-alpha at 24 h than MN (p < 0.01). Production of IL-10 by LPS-stimulated AM was sixfold lower than MN (p < 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 abi lity to produce TGF-alpha and IL-10 may favor a timely and regulated h ost response to inhaled pathogens while limiting potentially deleterio us inflammatory responses.