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)

Bromelain is a natural proteinase preparation derived from pineapple stem that is marketed for oral use as a digestive aid and as an antiinflammatory agent. Bromelain treatment in vitro has been previously shown to selectively remove certain cell surface molecules that may affect lymphocyte migration and activation. This study reports the effects of bromelain on a broad range of cell surface molecules and on lymphocytes, monocytes, and granulocytes under physiologically relevant conditions. In vitro bromelain treatment of leukocytes in whole blood proteolytically altered 14 of 59 leukocyte markers studied. Constitutively expressed bromelain-sensitive molecules included CD7, CD8alpha, CD14, CD16, CD21, CD41, CD42a, CD44, CD45RA, CD48, CD57, CD62L, CD128a, and CD128b. The proteolytic effect of bromelain increased as the concentration of plasma decreased, with EC50 ranging from >1000 microg/ml for 100% plasma to approximately 1 microg/ml in the absence of plasma, indicating the presence of an inhibitor of bromelain in plasma. alpha2-macroglobulin purified from plasma mimicked the inhibitory effect of whole plasma on bromelain activity. If proteolysis is required for the antiinflammatory actions of oral bromelain, these data suggest that the required concentrations are more likely to be achieved locally in the gastrointestinal tract or in other tissue sites where the plasma concentration is low, rather than in the bloodstream. The cell surface molecules altered by bromelain are involved in leukocyte homing and cellular adhesion and activation. Thus bromelain could potentially exert an antiinflammatory effect by multiple mechanisms, including alterations in leukocyte migration and activation.
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PMID:Bromelain treatment alters leukocyte expression of cell surface molecules involved in cellular adhesion and activation. 1216 79

The image of alpha2-macroglobulin is based on a paradigm evolved in the 1970s. During this decade alpha2-macroglobulin was shown to irreversibly entrap and thereby inhibit a maximum of two proteases. Additional binding of nonproteolytic proteins, i.e., inflammatory mediators and growth factors, is dependent on the conformational status of alpha2-macroglobulin. It was our aim to clarify whether the interaction of nonproteolytic proteins with alpha2-macroglobulin during inflammatory conditions might also modulate the capacity of alpha2-macroglobulin to inhibit proteases. To explore this possibility, bromelain, an exogenous protease, was titrated against plasma of critically ill or septic patients, whose pathophysiological conditions are defined by a massive release of inflammatory mediators. The stoichiometry of bromelain inhibition by alpha2-macroglobulin was quantified by caseolytic activity assays. The maximal alpha2-macroglobulin/bromelain inhibition ratios were significantly increased (1:6 and 1:8 in the two patient groups, P < 0.01) as compared with control groups (1:2 with purified alpha2-macroglobulin and 1:4 in healthy volunteers). The increase of alpha2-macroglobulin inhibition capacity in patients was paralleled by the appearance of a large signal on Western blots, suggesting the formation of additional complexes. Our results demonstrate alpha2-macroglobulin to have more flexibility than had been thought, and it may thereby contribute to a shift in a 30-year-old paradigm.
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PMID:The capacity of alpha2-macroglobulin to inhibit an exogenous protease is significantly increased in critically ill and septic patients. 1520 96