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.
Marsik
Claudia
C
Department of Clinical Pharmacology, Division of Immunology and Hematology, and Clinical Institute of Medical and Chemical Laboratory Diagnostics, Vienna University, Vienna, Austria.
Mayr
Florian
F
Cardona
Francesco
F
Schaller
Georg
G
Wagner
Oswald F
OF
Jilma
Bernd
B
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