C5a-induced migration of human monocytes is primed by dexamethasone.
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.
Pieters
W R
WR
Department of Pulmonary Diseases, University Hospital Utrecht, The Netherlands.
Houben
L A
LA
Koenderman
L
L
Raaijmakers
J A
JA
D015703:Antigens, CD / Q000032:analysis; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D002633:Chemotaxis / Q000187:drug effects*; D015936:Complement C5a / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology*; D004357:Drug Synergism; D006801:Humans; D009000:Monocytes / Q000187:drug effects*; D011994:Recombinant Proteins / Q000494:pharmacology; D015854:Up-Regulation
D015703:Antigens, CD; D011994:Recombinant Proteins; D003907:Dexamethasone; D015936:Complement C5a