Abstract
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.
Highlights
Inflammation is a complex physiological process involving numerous receptor-ligand interactions between leukocytes and the endothelial lining of the blood vessel that lead to the trafficking of leukocyte subsets throughout the body [1]
The results reveal a site-specific proteolysis through which bromelain treatment abolishes interactions between neutrophils and immobilized P-selectin, but not E-selectin, under conditions of physiological shear stress in vitro, suggesting another molecular mechanism through which bromelain may act as an anti-inflammatory agent
We found that bromelain treatment of neutrophils nearly eliminated their ability to interact with P-selectin presented on substrates in vitro, while E-selectin-mediated interactions are unaffected
Summary
Inflammation is a complex physiological process involving numerous receptor-ligand interactions between leukocytes and the endothelial lining of the blood vessel that lead to the trafficking of leukocyte subsets throughout the body [1]. We utilized a photochemical surface modification strategy [14] developed in our lab to generate substrates presenting controlled densities of P-selectin or E-selectin [15], and used these substrates to investigate the effect of bromelain treatment on the ability of human neutrophils to tether and roll in flow assays (Figure 1).
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