Bromelain decreases neutrophil interactions with P-selectin, but not E-selectin, in vitro by proteolytic cleavage of P-selectin glycoprotein ligand-1.
Stem bromelain, a cysteine protease isolated from pineapples, is a natural anti-inflammatory treatment, yet its mechanism of action remains unclear. Curious as to whether bromelain might affect selectin-mediated leukocyte rolling, we studied the ability of bromelain-treated human neutrophils to tether to substrates presenting immobilized P-selectin or E-selectin under shear stress. Bromelain treatment attenuated P-selectin-mediated tethering but had no effect on neutrophil recruitment on E-selectin substrates. Flow cytometric analysis of human neutrophils, using two antibodies against distinct epitopes within the P-selectin glycoprotein ligand-1 (PSGL-1) active site, revealed that bromelain cleaves PSGL-1 to remove one of two sites required for P-selectin binding, while leaving the region required for E-selectin binding intact. These findings suggest one molecular mechanism by which bromelain may exert its anti-inflammatory effects is via selective cleavage of PSGL-1 to reduce P-selectin-mediated neutrophil recruitment.
Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America.
Jessica M
JM
Banks
Christine T
CT
Herman
Ryan C
RC
Bailey
D001963:Bromelains / Q000494:pharmacology*; D019040:E-Selectin; D005260:Female; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D009504:Neutrophils / Q000166:cytology / Q000378:metabolism*; D019007:P-Selectin / Q000378:metabolism*; D059748:Proteolysis / Q000187:drug effects*
D019040:E-Selectin; D008562:Membrane Glycoproteins; D019007:P-Selectin; C084882:P-selectin ligand protein; C546936:SELE protein, human; D001963:Bromelains