Expression of complement alternative pathway proteins by endothelial cells. Differential regulation by interleukin 1 and glucocorticoids.
We have studied the secretion of proteins of the alternative pathway of complement C3, factor B and factor H by human umbilical vein endothelial cells (HUVEC). Results showed that factor H and factor B are quantitatively secreted in abundance whereas C3 could only be detected when the cells are maintained in culture during long periods of time. Interferon-gamma stimulated factor H, factor B and, to a lesser extent, C3 secretions. Interleukin (IL) 1 had a differential effect on spontaneous C3, factor B and factor H secretions. In the presence of IL 1, there was a significant secretion of C3 occurring within a short period of culture. IL 1 also stimulated factor B secretion. There was a synergistic stimulating effect between IL 1 and interferon-gamma to bring C3 and factor B productions by HUVEC to very high levels. In contrast, factor H secretion was consistently inhibited by IL 1. Local increase in C3 and factor B secretions by endothelial cells in the presence of IL 1 may have important implications in the inflammatory reaction. In striking contrast, the glucocorticoid dexamethasone (DXM) had modulatory effects which are consistent with its anti-inflammatory properties. DXM, at therapeutic concentrations, decreased C3 and factor B secretions and increased factor H secretion. Local modulation of complement protein secretion by DXM appears to be a new mechanism by which this glucocorticoid may control inflammation.
Dauchel
H
H
INSERM U-78, Bois-Guillaume, France.
Julen
N
N
Lemercier
C
C
Daveau
M
M
Ozanne
D
D
Fontaine
M
M
Ripoche
J
J
D003180:Complement C3b Inactivator Proteins / Q000378:metabolism; D015932:Complement C3c / Q000378:metabolism; D011415:Complement Factor B / Q000378:metabolism; D017242:Complement Factor H; D017244:Complement Factor I; D003170:Complement Pathway, Alternative / Q000502:physiology*; D003907:Dexamethasone / Q000494:pharmacology; D004727:Endothelium / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000494:pharmacology*; D012697:Serine Endopeptidases / Q000378:metabolism
C493495:CFH protein, human; D003180:Complement C3b Inactivator Proteins; D005938:Glucocorticoids; D007375:Interleukin-1; D003907:Dexamethasone; D015932:Complement C3c; D017242:Complement Factor H; D012697:Serine Endopeptidases; D017244:Complement Factor I; D011415:Complement Factor B