Development of a peptide inhibitor of hyaluronan-mediated leukocyte trafficking

Mark E. Mummert, Mansour Mohamadzadeh, Diana I. Mummert, Norikatsu Mizumoto, Akira Takashima

Research output: Contribution to journalArticlepeer-review

148 Scopus citations

Abstract

Hyaluronan (HA), a high molecular weight glycosaminoglycan, is expressed abundantly in the extracellular matrix and on cell surfaces. Although HA is known to bind many adhesion molecules, little information has been available with respect to its direct physiological role. In this study, we developed a novel 12-mer (GAHWQFNALTVR) peptide inhibitor of HA, termed 'Pep-1,' by using phage display technology. Pep-1 showed specific binding to soluble, immobilized, and cell-associated forms of HA, and it inhibited leukocyte adhesion to HA substrates almost completely. Systemic, local, or topical administration of Pep-1 inhibited the expression of contact hypersensitivity responses in mice by blocking skin-directed homing of inflammatory leukocytes. Pep-1 also inhibited the sensitization phase by blocking hapten-triggered migration of Langerhans cells from the epidermis. These observations document that HA plays an essential role in 'two-way' trafficking of leukocytes to and from an inflamed tissue, and thus provide technical and conceptual bases for testing the potential efficacy of HA inhibitors (e.g., Pep-1) for inflammatory disorders.

Original languageEnglish (US)
Pages (from-to)769-779
Number of pages11
JournalJournal of Experimental Medicine
Volume192
Issue number6
DOIs
StatePublished - 2000
Externally publishedYes

Keywords

  • Contact hypersensitivity
  • Glycosaminoglycan
  • Langerhans cell
  • Leukocyte homing
  • Phage display

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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