Journal
BLOOD
Volume 115, Issue 23, Pages 4699-4706Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2009-07-230631
Keywords
-
Categories
Funding
- NIAID NIH HHS [R01 AI049264] Funding Source: Medline
Ask authors/readers for more resources
Src homology 2 domain-containing inositol 5-phosphatase (SHIP-/-) animals display an age-related increase in interleukin-6 (IL-6), a decrease in B lymphopoiesis, and an elevation in myelopoiesis. We investigated the origin of the IL-6 production and show that it is largely produced by peritoneal and splenic macrophages. IL-6 production by these macrophages is not a direct result of the loss of SHIP: IL-6 production is not spontaneous, is absent from bone marrow-derived macrophages, declines with prolonged culture of macrophages, and requires a stimulus present in vivo. The IL-6-rich peritoneal cavity of SHIP-/- mice shows more than 700-fold more immunoglobulin G (IgG) than wild-type, approximately 20% of which is aggregated or in an immune complex and contains B220(+) cells that secrete IgG. The SHIP-deficient peritoneal macrophages show evidence of IgG receptor stimulation. Animals lacking both the signal-transducing gamma-chain of IgG receptors and SHIP or Ig and SHIP produce less IL-6. The data indicate a feed-forward process in which peripheral macrophages, responding through IgG receptors to secreted IgG, produce IL-6, to support further B-cell production of IgG. Because of the proinflammatory phenotype of SHIP-/- animals, these findings emphasize the importance of IL-6-neutralizing strategies in autoimmune and proinflammatory diseases. (Blood. 2010;115(23):4699-4706)
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available