Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.22.32 (bromelain)
 1,025 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

L-selectin, the peripheral lymph node "homing receptor," is an adhesion protein that mediates lymphocyte binding to lymph node high endothelial venules. Ligands for this protein have been identified only on endothelial cells, and recent murine studies indicate that CD34 on endothelial cells is an L-selectin ligand. To investigate whether CD34 expressed on hematopoietic cells functions as an L-selectin ligand, we used an in vitro binding assay to examine lymphocyte adherence to KG1a, a CD34+ human hematopoietic progenitor cell line. We observed specific L-selectin-mediated adherence of lymphocytes to KG1a: the binding was calcium-dependent, was strictly inhibited by anti-L-selectin antibodies and by carbohydrate ligands of L-selectin, and was abrogated by induction of L-selectin shedding from the lymphocyte membrane by treatment with phorbol esters. However, blocking studies using anti-CD34 antibodies, and experiments using KG1a cells sorted for CD34 expression and COS-7 cells transfected with full-length CD34 cDNA indicate that the ligand on KG1a is not CD34; moreover, RPMI 8402, a CD34+ cell line, does not support lymphocyte adherence in the binding assay. Treatment of KG1a with the enzymes neuraminidase, chymotrypsin, and bromelain abrogated lymphocyte binding to the cells, indicating that the ligand is a glycoprotein. These experiments show that CD34 on hematopoietic cells is not an L-selectin ligand and provide the first evidence of a ligand for L-selectin present on a non-endothelial cell.
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PMID:Detection of an L-selectin ligand on a hematopoietic progenitor cell line. 752 35

Bromelain, a mixture of proteases derived from pineapple stem, has been reported to have therapeutic benefits in a variety of inflammatory diseases, including murine inflammatory bowel disease. The purpose of this work was to understand potential mechanisms for this anti-inflammatory activity. Exposure to bromelain in vitro has been shown to remove a number of cell surface molecules that are vital to leukocyte trafficking, including CD128a/CXCR1 and CD128b/CXCR2 that serve as receptors for the neutrophil chemoattractant IL-8 and its murine homologues. We hypothesized that specific proteolytic removal of CD128 molecules by bromelain would inhibit neutrophil migration to IL-8 and thus decrease acute responses to inflammatory stimuli. Using an in vitro chemotaxis assay, we demonstrated a 40% reduction in migration of bromelain- vs. sham-treated human neutrophils in response to rhIL-8. Migration to the bacterial peptide analog fMLP was unaffected, indicating that bromelain does not induce a global defect in leukocyte migration. In vivo bromelain treatment generated a 50-85% reduction in neutrophil migration in 3 different murine models of leukocyte migration into the inflamed peritoneal cavity. Intravital microscopy demonstrated that although in vivo bromelain treatment transiently decreased leukocyte rolling, its primary long-term effect was abrogation of firm adhesion of leukocytes to blood vessels at the site of inflammation. These changes in adhesion were correlated with rapid re-expression of the bromelain-sensitive CD62L/L-selectin molecules that mediate rolling following in vivo bromelain treatment and minimal re-expression of CD128 over the time period studied. Taken together, these studies demonstrate that bromelain can effectively decrease neutrophil migration to sites of acute inflammation and support the specific removal of the CD128 chemokine receptor as a potential mechanism of action.
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PMID:Bromelain treatment decreases neutrophil migration to sites of inflammation. 1848 69