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Enhanced Development of Functional Murine Mast Cells in Human Stem Cell Factor Transgenic Immune-Deficient Mice
Saturday, March 5, 2016
South Exhibit Hall H (Convention Center)
Kshitij Gupta, PhD, Hariharan Subramanian, PhD, Hydar Ali, PhD
Rationale:

Previous studies have shown that engraftment of human CD34+ hematopoietic stem cells (hHSC) into immune-deficient NGS (NOD, SCID, IL2 receptor γ-null) mice transgenic for membrane-bound human stem cell factor (hSCF-NSG, “humanized mice”) results in the robust development of human mast cells. Here, we sought to determine if naïve NSG mice without hHSC engraftment develop endogenous mast cells and if this response is modulated in hSCF-NSG mice.

Methods:

Peritoneal lavage and skin slices of NSG and hSCF-NSG mice were stained with toluidine blue. Peritoneal mast cells were primed with IgE and the effects of antigen and antimicrobial peptide LL-37 on degranulation was determined. Passive cutaneous anaphylaxis (PCA) was performed with antigen in IgE-sensitized mice and increased vascular permeability was determined.

Results: Peritoneal lavage of NSG mice contained mast cells and this was enhanced by >4-fold in hSCF-NSG mice. Skin slices of NSG mice showed the presence of 18 ± 4 mast cells per high power field (200X) but this was increased to 36 ± 6 in hSCF-NSG mice. NSG mice developed PCA in response to antigen but this response was increased by 3.2-fold in hSCF-NSG mice.

Conclusions:

Results presented herein suggest that previously developed humanized mice likely contain both human and murine mast cells, thus compromising their usefulness to study human mast cell function in vivo. However, the enhanced development of murine mast cells in naïve hSCF-NSG mice without hHSC engraftment provides a new model to study the role of mast cells on allergic responses in vivo.