title: The multiple chemokine-binding bovine herpesvirus 1 glycoprotein G (BHV1gG) inhibits polymorphonuclear cell but not monocyte migration into inflammatory sites.
abstract: Chemokines facilitate the recruitment of inflammatory cells into tissues, contributing to target organ injury in a wide range of inflammatory and autoimmune diseases. Targeting either single chemokines or chemokine receptors alters the progression of disease in animal models of rheumatoid arthritis and lupus with varying degrees of efficacy but clinical trials in humans have been less successful. Given the redundancy of chemokine-chemokine receptor interactions, targeting of more than one chemokine may be required to inhibit active inflammatory disease. To test the effects of multiple-chemokine blockade in inflammation, we generated an adenovirus expressing bovine herpesvirus 1 glycoprotein G (BHV1gG), a viral chemokine antagonist that binds to a wide spectrum of murine and human chemokines, fused to the Fc portion of murine IgG2a. Administration of the adenovirus significantly inhibited thioglycollate-induced migration of polymorphonuclear leukocytes into the peritoneal cavity of BALB/c mice and reduced both clinical severity and articular damage in K/BxN serum transfer-induced arthritis. However, treatment with BHV1gG-Ig fusion protein did not prevent monocyte infiltration into the peritoneum in the thioglycollate model and did not prevent renal monocyte infiltration or nephritis in lupus-prone NZB/W mice. These observations suggest that the simultaneous inhibition of multiple chemokines by BHV1gG has the potential to interfere with acute inflammatory responses mediated by polymorphonuclear leukocytes, but is less effective in chronic inflammatory disease mediated by macrophages.
authors: Center for Genomics and Human Genetics, The Feinstein Institute for Medical Research, Manhasset, New York, NY 11030.
authors: Zheng
authors: Z
authors: Liu
authors: Ramalingam
authors: R
authors: Bethunaickan
authors: Ranjit
authors: R
authors: Sahu
authors: Max
authors: M
authors: Brenner
authors: Teresina
authors: T
authors: Laragione
authors: Percio S
authors: PS
authors: Gulko
authors: Anne
authors: A
authors: Davidson
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology / Q000517:prevention & control; D002118:Calcium / Q000276:immunology / Q000378:metabolism; D002417:Cattle; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology*; D018925:Chemokines / Q000378:metabolism; D007242:Herpesvirus 1, Bovine / Q000235:genetics; D007106:Immune Sera / Q000276:immunology; D007141:Immunoglobulin Fc Fragments / Q000235:genetics / Q000276:immunology; D007249:Inflammation / Q000276:immunology* / Q000378:metabolism; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D016513:Mice, SCID; D009000:Monocytes / Q000187:drug effects / Q000276:immunology*; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology*; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000276:immunology / Q000494:pharmacology; D013864:Thioglycolates / Q000276:immunology / Q000494:pharmacology; D014764:Viral Proteins / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology
chemical_list: D018925:Chemokines; D007106:Immune Sera; D007141:Immunoglobulin Fc Fragments; D011993:Recombinant Fusion Proteins; D013864:Thioglycolates; D014764:Viral Proteins; C046998:bovine herpesvirus type-1 glycoproteins; D002118:Calcium
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