Am. J. Respir. Cell Mol. Biol., Vol 12, No. 6, Jun 1995, 691-696.
C5a-induced migration of human monocytes is primed by dexamethasone
WR Pieters, LA Houben, L Koenderman and JA Raaijmakers
Department of Pulmonary Diseases, University Hospital Utrecht, The Netherlands.
Allergic inflammation in the lung is characteristic of allergic asthma.
This inflammatory process is inhibited by treatment with glucocorticoids.
One of the cell types involved in the inflammatory process, the monocyte,
is found in enhanced numbers in mucosal lung biopsies of asthmatic
patients. Little is known about the mechanisms that lead to increased
numbers of monocytes in lung tissue. We studied one of the processes
involved, chemotaxis, in a modified Boyden Chamber assay. The effect of the
antiinflammatory drug dexamethasone was tested on monocyte chemotactic
responses to complement fragment C5a. Human monocytes from peripheral blood
of normal human volunteers were purified by centrifugal elutriation. The
monocytes showed a reproducible chemotactic response toward C5a with an
optimum at a concentration of 10(-9) M. After culture of the monocytes
overnight, the monocyte responses were clearly impaired. It is interesting
that upon culture, dexamethasone increased monocyte chemotaxis in a dose-
dependent manner. Analysis of the filters with an image analyzer showed
that the effect was not through modulation of a subpopulation of monocytes.
This steroid effect was specific and modulated via steroid receptors,
because the introduction of RU 38486, a steroid receptor antagonist,
completely inhibited the effect of dexamethasone. These findings are a
further illustration of the complex mechanisms involved in the
orchestration of the inflammatory response in asthma.
