gp49B1 deficiency is associated with increases in cytokine and chemokine production and severity of proliferative synovitis induced by anti-type II collagen mAb.

Abstract

Mice with a disrupted gp49B gene, which encodes gp49B1 that is expressed on certain hematopoietic cells and has two immunoreceptor tyrosine-based inhibitory motifs (ITIM), exhibit augmented FcepsilonRI-initiated mast cell degranulation and resultant tissue edema. gp49B1-deficient (gp49B(-/-)) mice also exhibit exaggerated lipopolysaccharide (LPS)-induced intravascular neutrophil aggregation leading to cutaneous microangiopathy. To determine whether gp49B(-/-) mice exhibit elevated cytokine and chemokine levels leading to pathologic inflammation, we quantified clinical and morphologic parameters of arthritis and tissue levels of contributory mediators in gp49B(-/-) and gp49B1-sufficient (gp49B(+/+)) mice injected with anti-type II collagen monoclonal antibody (mAb) and LPS. Clinical scores for joint swelling and histological assessments of synovial thickness and cartilage matrix depletion at day 7 were significantly 2.3- to 2.5-fold greater and were more prolonged in gp49B(-/-) mice. At day 5, the amounts of IL-1beta, macrophage inflammatory protein (MIP)-1alpha, and MIP-2 were 2.1-, 2.5-, and 12-fold greater in joint extracts from gp49B(-/-) mice. A significant 2.7-fold more neutrophils infiltrated the synovium of gp49B(-/-) mice at day 7, and neutrophilia persisted with the delayed resolution of the synovitis. mAb-mediated depletion of neutrophils prevented the synovitis in both strains. Thus, gp49B1 counter-regulates the cytokine and chemokine induction and attendant neutrophilia that are all essential for synovitis and cartilage matrix depletion.

• Authors: Joseph S Zhou, Daniel S Friend, David M Lee, Lin Li, K Frank Austen, Howard R Katz
• Journal: European journal of immunology (Eur J Immunol) Vol. 35 Issue 5 Pg. 1530-8 (May 2005) ISSN: 0014-2980 [Print] Germany
• PMID: 15827966 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antibodies, Monoclonal
• Collagen Type II
• Cytokines
• Lilrb4 protein, mouse
• Membrane Glycoproteins
• Receptors, Immunologic

Topics

• Animals
• Antibodies, Monoclonal (pharmacology)
• Collagen Type II (immunology)
• Cytokines (biosynthesis, immunology)
• Mast Cells (immunology)
• Membrane Glycoproteins (deficiency)
• Mice
• Neutrophil Infiltration (immunology)
• Receptors, Immunologic (deficiency)
• Synovitis (chemically induced, immunology, pathology)