In vivo targeting of activated leukocytes by a β2-integrin binding peptide

Mol Diagn Ther. 2014 Feb;18(1):39-44. doi: 10.1007/s40291-013-0052-5.

Abstract

Background: In immunopathological conditions, clinical diagnosis is commonly made on the basis of patient symptoms, measurement of blood leukocyte levels or proinflammatory biomarkers, non-specific radiological findings and, regarding infection, microbiological analysis. Nevertheless, frequently the exact spatial location of inflammation or even infection cannot be reliably identified, despite the use of up-to-date clinical, laboratory and imaging techniques. For this reason, new tools are warranted for use in advanced diagnosis and therapy targeting in patients.

Objective: The peptide CPCFLLGCC (LLG), known to bind activated β2-integrins in vitro, was fused with green fluorescent protein (GFP) to test the ability of LLG fusions to target and bind activated leukocytes in vivo.

Methods: A murine skin scratch inflammation model was chosen for the convenient non-surgical detection of GFP.

Results: The murine skin lesion inflammation model demonstrated in vivo targeting of LLG-GFP to sites of inflammation. Targeting by LLG-GFP fusion construct depends on the ability of the LLG-moiety to bind activated leukocytes. Control construct unable to bind β2-integrins appeared biologically inert.

Conclusion: The data support the possibility of using this fluorescently labeled peptide as a tool for both the detection of and targeting to inflammatory sites characterized by robust leukocyte activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD18 Antigens / immunology
  • CD18 Antigens / metabolism*
  • Cell Line
  • Disease Models, Animal
  • Drug Delivery Systems / methods*
  • Humans
  • Inflammation / immunology*
  • Leukocytes / cytology*
  • Leukocytes / immunology
  • Leukocytes / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Peptides / chemistry*
  • Peptides / metabolism*
  • Recombinant Fusion Proteins / metabolism*

Substances

  • CD18 Antigens
  • Peptides
  • Recombinant Fusion Proteins