Am. J. Respir. Cell Mol. Biol., Vol 17, No. 2, 08 1997, 218-226.
Inability of histamine to regulate TNF-alpha production by human alveolar macrophages
J Rowe, JJ Finlay-Jones, TE Nicholas, J Bowden, S Morton and PH Hart
Department of Microbiology and Infectious Diseases, School of Medicine, Flinders University of South Australia, Adelaide. pmnjur@pippin.cc.flinders.edu.au
Tumor necrosis factor alpha (TNF-alpha), a major product of alveolar
macrophages (AM), has been implicated in many pulmonary diseases.
Histamine, a mediator important in pulmonary inflammation, has been
demonstrated to regulate the production of TNF-alpha by monocytes. In this
study, we show that human AM and monocytes differ in their responses to
histamine. Whereas histamine suppressed lipopolysaccharide (LPS)-stimulated
TNF-alpha production by monocytes through a cAMP- dependent mechanism, it
had no effect on either cAMP levels or TNF- alpha production by AM. In
contrast, both PGE2 and IL-10 suppressed LPS- stimulated TNF-alpha
production by AM and monocytes. The lack of response of AM to histamine
appears unique, as histamine suppressed LPS- stimulated TNF-alpha
production by mononuclear cells isolated from sites of acute and chronic
inflammation, as well as from noninflammatory tissues, and by macrophages
differentiated in vitro. In the presence of the phosphodiesterase (PDE)
inhibitor 3-isobutyl-1- methylxanthine, histamine increased cAMP levels in
AM. Freshly isolated monocytes and AM did not differ in PDE activity.
However, PDE activity in AM, but not in monocytes, was increased 15 min
after culture with histamine and may, in part, be responsible for the
inability of histamine to suppress TNF-alpha production by AM. However,
this increase was small and we hypothesize that additional mechanisms may
contribute to the unresponsiveness of AM to histamine. We suggest that the
lack of response of AM to histamine may be important in the host defense
function of AM in the distal lung.
