E-selectin ligands mediate tumor necrosis factor-induced neutrophil sequestration and pulmonary edema in guinea pig lungs

Circulation Research
S K LoA B Malik

Abstract

We have previously shown in perfused guinea pig lungs that tumor necrosis factor-alpha (TNF-alpha) pretreatment of lungs enhanced neutrophil sequestration as reflected by a 2.4-fold increase in lung myeloperoxidase (MPO) activity. Subsequent perfusion of phorbol 12-myristate 13-acetate (PMA) to activate the sequestered neutrophils produced an approximately threefold increase in the pulmonary capillary hydrostatic pressure and fulminant pulmonary edema. Using this ex vivo model of lung injury, we studied the role of three putative E-selectin ligands, sialyl-Lewis X, Lewis X, and dimeric sialyl-Lewis X, in mediating neutrophil sequestration and pulmonary edema. We pretreated neutrophils with monoclonal antibodies (mAbs) directed against these E-selectin ligands. Pretreatment of neutrophils with mAbs to sialyl-Lewis X and Lewis X reduced the neutrophil sequestration, as evidenced by 45% and 27% reductions in MPO activity from control levels, respectively. This occurred in parallel with inhibition of neutrophil adhesion to the TNF-alpha-activated endothelial cells in vitro. The mAbs to dimeric sialyl-Lewis X and an isotype-matched control mAb against lactosamines present on neutrophils had no effect on lung MPO activity and neutrop...Continue Reading

References

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Citations

Jan 1, 1996·International Journal of Clinical & Laboratory Research·G BertonC A Lowell
Jan 31, 2002·Journal of Veterinary Internal Medicine·Z A RadiM R Ackermann
Aug 6, 2005·American Journal of Respiratory and Critical Care Medicine·Kieran P O'DeaMasao Takata
Jun 6, 2000·American Journal of Respiratory Cell and Molecular Biology·R J KanerR G Crystal
Dec 29, 2010·Journal of Cardiovascular Disease Research·Guang YangRudolf Lucas
Feb 25, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Phoebe LinRichard D Ye
Jan 23, 2018·Frontiers in Immunology·Jürg HamacherUz Stammberger

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