Human granulocyte CD11b expression as a pharmacodynamic biomarker of inflammation.
A method has been developed for the direct quantification of the CD11b integrin on granulocytes by flow cytometric analysis of whole blood specimens following either LTB(4) or lipopolysaccharide (LPS) stimulation. This method has utility in evaluating the pharmacodynamic action of either LTB(4) receptor antagonists or immune cell modulators in effecting CD11b integrin expression and granulocyte activation in human subjects administered such drugs. Previous studies using CD11b as a biomarker of granulocyte activation have faltered because of the difficulty in controlling the activation state of the granulocyte following removal of blood from subjects. The present study has made use of a newly validated method using either LTB(4) or LPS to stimulate CD11b expression on granulocytes and has been used, as one measure, in the evaluation of LPS activity when administered to normal human volunteers.
Davis
H M
HM
SmithKline Beecham Pharmaceuticals, Pharmacodynamics and Exploratory Research Laboratory, Clinical Pharmacology Unit, Presbyterian Medical Center, Philadelphia, PA 19104, USA. hughdavis-1@sbphrd.com
Carpenter
D C
DC
Stahl
J M
JM
Zhang
W
W
Hynicka
W P
WP
Griswold
D E
DE
D000179:Acrylates / Q000494:pharmacology; D000276:Adjuvants, Immunologic / Q000494:pharmacology; D001667:Binding, Competitive; D005434:Flow Cytometry / Q000379:methods*; D006801:Humans; D007249:Inflammation / Q000175:diagnosis*; D016023:Integrins / Q000096:biosynthesis / Q000097:blood*; D007975:Leukotriene B4 / Q000494:pharmacology; D017998:Leukotriene D4 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D016177:Macrophage-1 Antigen / Q000096:biosynthesis / Q000097:blood*; D008297:Male; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology*; D011725:Pyridines / Q000494:pharmacology; D018102:Receptors, Leukotriene B4 / Q000037:antagonists & inhibitors
D000179:Acrylates; D000276:Adjuvants, Immunologic; D016023:Integrins; D008070:Lipopolysaccharides; D016177:Macrophage-1 Antigen; D011725:Pyridines; D018102:Receptors, Leukotriene B4; D007975:Leukotriene B4; D009240:N-Formylmethionine Leucyl-Phenylalanine; D017998:Leukotriene D4; C093304:Ticolubant