Bromelain Treatment Alters Leukocyte Expression of Cell Surface Molecules Involved in Cellular Adhesion and Activation

doi:10.1006/clim.2002.5254

Clinical Immunology

Volume 104, Issue 2, August 2002, Pages 183-190

https://doi.org/10.1006/clim.2002.5254 Get rights and content

Abstract

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, CD8α, 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 μg/ml for 100% plasma to ∼1 μg/ml in the absence of plasma, indicating the presence of an inhibitor of bromelain in plasma. α2-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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Several substances that have anti-inflammatory, antiproteinase, and anti-infective properties have been evaluated as modulators of the inflammatory response in periodontal disease. However, evidence for the anti-inflammatory and antioxidative activities of bromelain is limited. This study evaluated the impact of systemically administered bromelain on the progression of experimental periodontitis.
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It has anti-inflammatory properties whose effects on IBD, especially in UC, have been the subject of many studies. Studies have reported that bromelain has an anti-inflammatory effect on in vivo IBD murine models and in vitro T-cell activation and cytokine secretion due to its proteolytic activity (Mynott et al., 2002; Hale et al., 2002). The main mechanism of action of bromelain appears to be proteolytic.
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Although we cannot discard the presence of serum stem bromelain concentrations lower than 30 ng/mL, due to limitation of the employed assay, an eventual undetectable level might not be adequate for the proteolysis of a significant amount of stem bromelain substrates after the blood access. In fact, stem bromelain concentrations greater than 500 μg/mL are required to surpass the alpha-2-macroglobulin inhibition in the blood [45]. Taken together, these data demonstrate that the anti-nociceptive effect of orally administered stem bromelain may likely reflect its local proteolytic activity within the jejunum tract, rather than a systemic response.
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Regular ArticleBromelain Treatment Alters Leukocyte Expression of Cell Surface Molecules Involved in Cellular Adhesion and Activation

Abstract

Arch. Biochem. Biophys.

J. Renal Nutr.

J. Autoimmun.

FEBS Lett.

Hematol. Oncol. Clin. North Am.

Curr. Opin. Immunol.

Microbes Infect.

Semin Immunol.

Bromelain: A literature review and discussion of its therapeutic applications

Altern. Med. Rev.

Intestinal absorption of undegraded proteins in men: Presence of bromelain in plasma after oral intake

Am. J. Physiol.

Effects of an orally active non-peptide bradykinin B2 receptor antagonist, FR173657, on plasma exudation in rat carrageenin-induced pleurisy

Br. J. Pharmacol.

Determination of bradykinin-(1-5) in inflammatory exudate by a new ELISA as a reliable indicator of bradykinin generation

Inflammation Res.

Increased migration of neutrophils to granulocyte-colony stimulating factor in rat carrageenin-induced pleurisy: Roles of complement, bradykinin, and inducible cyclooxygenase-2

Inflammation Res

Beneficial effect of proteases on allograft arteriosclerosis in a rat aortic model

Nephrol. Dial. Transplant.

Natural treatment of perennial allergic rhinitis

Altern. Med. Rev.

Use of bromelain for mild ulcerative colitis

Ann. Intern. Med.

Bromelain treatment of human T cells removes CD44, CD45RA, E2/MIC2, CD6, CD7, CD8, and Leu 8/LAM1 surface molecules and markedly enhances CD2-mediated T cell activation

J. Immunol.

Bromelain, from pineapple stems, proteolytically blocks activation of extracellular regulated kinase-2 in T cells

J. Immunol.

Effects of oral bromelain administration on the impaired immunocytotoxicity of mononuclear cells from mammary tumor patients

Oncol. Rep.

Regular Article
Bromelain Treatment Alters Leukocyte Expression of Cell Surface Molecules Involved in Cellular Adhesion and Activation