Adenoviral-mediated delivery of a viral chemokine binding protein blocks CC-chemokine activity in vitro and in vivo

Christina A. Bursill, Shijie Cai, Keith M. Channon, David R. Greaves

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Chemokines are important mediators of leukocyte recruitment and activation that play critical roles in the pathology of inflammatory diseases such as atherosclerosis, rheumatoid arthritis and asthma. The vaccinia virus (strain Lister) expresses a 35 kDa soluble protein ('35K') that binds and inactivates a wide range of CC chemokines. We generated a recombinant adenovirus encoding soluble 35K (Ad35K). Ad35K-infected cell culture medium, containing recombinant 35K, potently reduced migration of CCR5-transfected 293 cells by 95% in response to the CC-chemokine RANTES, but had no effect on cells transfected with the CX3CR1 fractalkine receptor. Delivery of Ad35K to mice in vivo via tail vein injection resulted in expression of recombinant 35K in plasma and increased serum RANTES and MIP-1α levels when quantified by ELISA. However, chemotaxis of both CCR5-transfected cells and primary macrophages was inhibited by more than 90% by plasma from Ad35K-infected animals compared with control plasma from animals injected with AdGFP. Furthermore, 35K delivered by intra-peritoneal injection more than halved biogel-induced inflammatory cell recruitment in peritoneal exudates compared to AdGFP medium. These studies identify broad-spectrum CC-chemokine blockade using in vivo adenoviral-mediated recombinant 35K expression as a promising strategy to reduce local and systemic inflammation.

LanguageEnglish
Pages187-196
Number of pages10
JournalImmunobiology
Volume207
Issue number3
DOIs
Publication statusPublished - 1 Jan 2003
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Hematology

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