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Bromelain treatment decreases neutrophil migration to sites of inflammation.

Publication ,  Journal Article
Fitzhugh, DJ; Shan, S; Dewhirst, MW; Hale, LP
Published in: Clin Immunol
July 2008

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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Published In

Clin Immunol

DOI

EISSN

1521-7035

Publication Date

July 2008

Volume

128

Issue

1

Start / End Page

66 / 74

Location

United States

Related Subject Headings

  • Neutrophils
  • Mice, Inbred BALB C
  • Mice
  • Inflammation
  • Immunology
  • Humans
  • Female
  • Chemotaxis, Leukocyte
  • Cells, Cultured
  • Cell Adhesion
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Fitzhugh, D. J., Shan, S., Dewhirst, M. W., & Hale, L. P. (2008). Bromelain treatment decreases neutrophil migration to sites of inflammation. Clin Immunol, 128(1), 66–74. https://doi.org/10.1016/j.clim.2008.02.015
Fitzhugh, David J., Siqing Shan, Mark W. Dewhirst, and Laura P. Hale. “Bromelain treatment decreases neutrophil migration to sites of inflammation.Clin Immunol 128, no. 1 (July 2008): 66–74. https://doi.org/10.1016/j.clim.2008.02.015.
Fitzhugh DJ, Shan S, Dewhirst MW, Hale LP. Bromelain treatment decreases neutrophil migration to sites of inflammation. Clin Immunol. 2008 Jul;128(1):66–74.
Fitzhugh, David J., et al. “Bromelain treatment decreases neutrophil migration to sites of inflammation.Clin Immunol, vol. 128, no. 1, July 2008, pp. 66–74. Pubmed, doi:10.1016/j.clim.2008.02.015.
Fitzhugh DJ, Shan S, Dewhirst MW, Hale LP. Bromelain treatment decreases neutrophil migration to sites of inflammation. Clin Immunol. 2008 Jul;128(1):66–74.
Journal cover image

Published In

Clin Immunol

DOI

EISSN

1521-7035

Publication Date

July 2008

Volume

128

Issue

1

Start / End Page

66 / 74

Location

United States

Related Subject Headings

  • Neutrophils
  • Mice, Inbred BALB C
  • Mice
  • Inflammation
  • Immunology
  • Humans
  • Female
  • Chemotaxis, Leukocyte
  • Cells, Cultured
  • Cell Adhesion