title: SHIP-deficient, alternatively activated macrophages protect mice during DSS-induced colitis.
abstract: mϕ are heterogeneous in their functions, and although it is clear that inflammatory mϕ contribute to inflammation in IBDs, multiple lines of evidence suggest that M2a mϕ may offer protection during intestinal inflammation. In vivo SHIP-deficient mouse mϕ are M2a so SHIP-deficient mice provide a unique genetic model of M2a mϕ. Based on this, this study tested the hypothesis that SHIP-deficient, M2a mϕ protect mice from intestinal inflammation. The objectives were to compare the susceptibility of SHIP+/+ and SHIP-/- littermates with DSS-induced intestinal inflammation and to determine whether protection was mϕ-mediated and whether protection could be transferred to a susceptible host. We have found that SHIP-/- mice are protected during DSS-induced intestinal inflammation. SHIP-/- mice have delayed rectal bleeding and reduced weight loss, disruption of intestinal architecture, and immune cell infiltration during DSS-induced colitis relative to their WT littermates. Using liposome depletion of mϕ, we found that SHIP-/- mouse protection was indeed mϕ-mediated. Finally, we determined that SHIP-/- mϕ-mediated protection could be conferred to susceptible WT mice by adoptive transfer of M2a mϕ derived ex vivo. This study supports our hypothesis by demonstrating that SHIP-deficient, M2a mϕ are protective in this murine model of acute intestinal inflammation. Adoptive transfer of M2a mϕ to patients with IBDs offers a promising, new strategy for treatment that may be particularly useful in patients who are otherwise refractory to conventional therapies.
authors.affiliation: Department of Pediatrics, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Shelley B
authors.initials: SB
authors.lastname: Weisser
authors.forename: Hayley K
authors.initials: HK
authors.lastname: Brugger
authors.forename: Nicole S
authors.initials: NS
authors.lastname: Voglmaier
authors.forename: Keith W
authors.initials: KW
authors.lastname: McLarren
authors.forename: Nico
authors.initials: N
authors.lastname: van Rooijen
authors.forename: Laura M
authors.initials: LM
authors.lastname: Sly
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D003092:Colitis / Q000139:chemically induced / Q000473:pathology* / Q000517:prevention & control*; D003106:Colon / Q000166:cytology / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D016264:Dextran Sulfate / Q000633:toxicity*; D005260:Female; D007124:Immunoenzyme Techniques; D007249:Inflammation / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D000072181:Inositol Polyphosphate 5-Phosphatases; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010744:Phosphoric Monoester Hydrolases / Q000502:physiology*
chemical_list: D016207:Cytokines; D016264:Dextran Sulfate; D010744:Phosphoric Monoester Hydrolases; D000072181:Inositol Polyphosphate 5-Phosphatases