ICMI 2015

T.92 Transfer of alternatively activated macrophages attenuates DNBS colitis independent of CCR2 or CX3CR1

Thursday, July 16, 2015
Grand Hall and Gallery, Ground Floor & 1st Floor (Maritim Hotel)
Gabriella Leung , University of Calgary, Calgary, AB, Canada
Arthur Wang, MSc , University of Calgary, Calgary, AB, Canada
Derek McKay, PhD , University of Calgary, Calgary, AB, Canada
Alternatively activated macrophages (AAM) are considered anti-inflammatory cells.  A transfer of AAMs has been shown to protect against experimental colitis.  Our HYPOTHESIS is that transferred AAMs protect against colitis via CCR2-dependent migration to the gut.

METHODS.  Bone marrow macrophages were stimulated with IL-4 for 48hr to induce alternative activation.  In vitro, the polarisation of WT, CCR2-KO, and CX3CR1-KO macrophages were compared phenotypically (PCR, flow cytometry) and functionally (arginase activity, nitric oxide production, cytokine secretion).  In vivo, the ability of WT and KO AAMs were tested in their ability to block DNBS colitis.  Cells were administered ip to WT mice 2d prior to the induction of colitis; mice were necropsied 3d later.

RESULTS.  The lack of CCR2 or CX3CR1 did not impair the ability of macrophage to alternatively activate as observed by AAM mRNA expression of Arg1, Ym1, Retnla.  AAMs were also similar in their functional parameters.  In mice, both WT and KO transferred AAMs afforded protection against DNBS colitis as demonstrated by reduced colon shortening and reduced macroscopic/microscopic damage scores.

DISCUSSION.  These data show that ip-transferred AAMs protect against DNBS colitis and do not require the expression of CCR2 or CX3CR1 to do so.  As a treatment for inflammatory bowel disease, the results suggest that AAMs may be an effective therapy even in the absence of these chemokine receptors.