Endotoxin down-modulates P-selectin glycoprotein ligand-1 (PSGL-1, CD162) on neutrophils in humans.
P-selectin glycoprotein ligand-1 (PSGL-1, CD162), the counter-receptor for P-selectin and possibly E- and L-selectin, mediates rolling of leukocytes during inflammation and, thus, plays a pivotal role in hemostasis and inflammation. PSGL-1 is constitutively expressed on circulating leukocytes. Until recently, PSGL-1 has been considered not to be regulated upon cell activation. As modulation of PSGL-1 has only recently been reported for three proinflammatory substances, PSGL-1 regulation was examined during systemic inflammation in humans. Nine healthy human volunteers received a bolus of 2 ng/kg LPS i.v. Endotoxin infusion down-modulated PSGL-1 expression on neutrophils, with a maximum at 6-8 hr (-22%; P =0.001 vs. baseline and placebo), which correlated with peak neutrophilia. Similar PSGL-1 down-regulation was observed on monocytes. sPSGL-1 plasma levels increased trendwise after LPS infusion (+12% at 6 hr; P =0.10). In vitro LPS stimulation of whole blood significantly down-regulated PSGL-1 on neutrophils (-43%) and monocytes (-35%) as early as 2 hr ( P <0.05; n =5) in both EDTA and lepirudin anticoagulated samples. In summary, PSGL-1 is down-modulated on neutrophils and monocytes during endotoxemia in humans. PSGL-1 down-regulation could potentially facilitate the development of neutrophilia.
Department of Clinical Pharmacology, Division of Immunology and Hematology, and Clinical Institute of Medical and Chemical Laboratory Diagnostics, Vienna University, Vienna, Austria.
Claudia
C
Marsik
Florian
F
Mayr
Francesco
F
Cardona
Georg
G
Schaller
Oswald F
OF
Wagner
Bernd
B
Jilma
D000704:Analysis of Variance; D015536:Down-Regulation; D019446:Endotoxemia / Q000276:immunology / Q000378:metabolism*; D004731:Endotoxins / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism*; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism*; D013997:Time Factors
D004731:Endotoxins; D008562:Membrane Glycoproteins; C084882:P-selectin ligand protein