C5a, interleukin-8 and tumour necrosis factor-alpha-induced changes in granulocyte and monocyte expression of complement receptors in whole blood and on isolated leukocytes.
Treatments targeting complement receptors have been demonstrated to improve outcome in experimental sepsis. The regulation of the complement receptors in sepsis is not clear. Lipopolysaccharide (LPS) stimulation of granulocytes ex vivo has been shown to reduce C5a receptor (CD88) expression and to increase CD35 and CD11b/CD18 expressions in whole blood but not on isolated cells, indicating an indirect effect mediated via factors in the blood. With the aim to study whether these effects could be attributed to C5a, tumour necrosis factor (TNF)-alpha and interleukin (IL)-8, whole blood or isolated granulocytes and monocytes from healthy individuals were investigated. After incubation with C5a in a dose range of 1 x 10(-9)-1 x 10(-7) mol/l, and TNF-alpha and IL-8 at doses of 1-100 ng/ml, the expressions of the complement receptors CD88, CD35, CD11b/CD18 were analysed by flow cytometry. Incubation with C5a reduced granulocyte CD88 expression by 44+/-6.9% and 82+/-4.2%, whereas monocyte CD88 expression decreased by 21+/-4.0 and 30+/-17% (whole blood and isolated cells). IL-8 and TNF-alpha incubation of granulocytes induced similar results. Granulocyte CD35 expression was significantly increased by 367, 175 and 336% by C5a, TNF-alpha, IL-8, respectively; CD11b expression was similarly increased. Consistent with findings in septic patients and after LPS incubation, it is concluded that all stimuli reduced granulocyte CD88 expression, whereas CD35 and CD11b were increased.
Furebring
M
M
Section of Infectious Diseases, Department of Medical Science, Uppsala University Hospital, Sweden. mia.furebring@medsci.uu.se
Håkansson
L
L
Venge
P
P
Sjölin
J
J
D000328:Adult; D018845:CD11 Antigens / Q000097:blood; D015936:Complement C5a / Q000494:pharmacology*; D015870:Gene Expression; D006098:Granulocytes / Q000378:metabolism; D006801:Humans; D016209:Interleukin-8 / Q000494:pharmacology*; D007962:Leukocytes / Q000378:metabolism; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D044087:Receptor, Anaphylatoxin C5a / Q000097:blood*; D011951:Receptors, Complement / Q000378:metabolism*; D017463:Receptors, Complement 3b / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D018845:CD11 Antigens; D016209:Interleukin-8; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement; D017463:Receptors, Complement 3b; D014409:Tumor Necrosis Factor-alpha; D015936:Complement C5a