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Substance P (subP) Suppresses Induction of Specific Memory IgE Responses By PBMC of Ragweed Sensitized IgE+ Humans, but NOT CD4+IL4+ or CD8+CD60+IL-4+ T CELLS or IL-4.
Monday, March 7, 2016
South Exhibit Hall H (Convention Center)
Bryan McCarthy, M.D., Charles J. Kim, BS, Seto M Chice, MS, Isabella DeGregorio, Vahe Amassian, MD, Mark Stewart, MD, PhD, Maja Nowakowski, PhD, Yitzchok M. Norowitz, BS, Tamar A. Smith-Norowitz, PhD, Rauno Joks, M.D., Helen G. Durkin, PhD
Rationale:

Transmagnetic/electrical stimulation of human/rat left temporo-parieto-occipital  cortex increases levels of the neuropeptide subP and CD4+ T cells  in blood while suppressing ongoing IgE responses; this was prevented by cutting rat spinal cord at T2 or thymectomy.  SubP suppresses murine memory IgE responses in vivo/vitro.  The signaling molecule p38MAPK is associated with IL-4 and CD4+ and CD8+CD60+T cells, IL-4 and 5 other cytokines (not IL-13) are required for human memory IgE responses.  The role of subP in suppression of human CD4+IL-4+ and CD8+CD60+IL-4+ T cells, p38MAPK+ leukocytes and memory IgE responses was investigated.

 Methods:

We determined the numbers of (l) CD4+IL-4+ and CD8+CD60±IL-4+ T cells and subP receptor+ (NK-1R) leukocyte subsets in blood of ragweed sensitized humans (n=6); (2) CD45+, CD4+CD3+, CD8+CD60±, CD19+, CD16/56+, and CD14+ cells expressing p38MAPK in PBMC ± 15-30 min incubation with PMA ± subP; and (3) the effect of subP on specific memory IgE responses by PBMC cultured for 0-12 days ± ragweed antigen ± subP ± antibodies to subP receptors (flow cytometry; ELISA) (data expressed as % T cell subsets, % total lymphocytes or monocytes, ng/ml)

Results:

SubP did not affect CD4+IL-4+ or CD8+CD60+IL-4+ T cells but suppressed CD45+p38MAPK+ lymphocytes (70%) (including CD4+,  CD8+, CD19+,  CD16/56+ p38MAPK+ cells), and specific memory IgE responses, with antibodies to subP receptors reversing this effect.  Monocytes, B and NK cells were subP receptor+ but T cells were not.

Conclusions:

Substance P suppresses specific memory IgE responses by acting on monocytes, B cells or NK cells, but not on T cells or IL-4.