Acidic Conditions Regulate Mast Cell Migration and Fc Epsilon RI–Mediated Cytokine Production
Saturday, March 5, 2016
South Exhibit Hall H (Convention Center)
Yosuke Kamide, MD, PhD, Tamotsu Ishizuka, MD, PhD, Hiroaki Hayashi, MD, Chihiro Mitsui, MD, Akio Mori, MD, PhD, Takeshi Hisada, MD, PhD, Kunio Dobashi, MD, PhD, Fumikazu Okajima, Masanobu Yamada, MD, PhD, Masami Taniguchi, MD, PhD
Rationale: The proton concentration or pH of blood is maintained at 7.4 ± 0.05, and inflammatory loci are associated with an acidic environment. The pH of exhaled breath condensate in patients with asthma is lower than that in healthy individuals, indicating that extracellular acidification contributes to the pathogenesis of allergosis. Therefore, we hypothesized that mast cells, which play a central role in allergosis, are regulated by acidic conditions. 

Methods: Mast cell migration was examined using the Boyden chamber technique. The MC/9 mouse mast cell clone sensitized with anti-dinitrophenyl (DNP) IgE was placed in the upper wells, and DNP-conjugated human serum albumin (DNP-HAS) was added to the lower wells. Mast cells in the lower wells were counted using a Fuchus Rosenthal calculator. DNP-IgE-sensitized MC/9 cells or bone-marrow derived mast cells (BMMCs) were incubated with DNP in pH-changed medium, and tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-13 levels in the supernatant were measured using enzyme-linked immunosorbent assays. The data were compared by using the Student’s t-test with the Bonferroni correction for multiple comparisons.

Results: Acidic pH significantly inhibited migration of MC/9 cells toward DNP-HAS. In addition, extracellular acidification clearly induced IL-6 and IL-13 production. The viability of MC/9 cells was not affected by alterations in pH.

Conclusions: Acidic pH inhibits MC/9 cell migration. Furthermore, extracellular acidification enhances DNP-IgEinduced IL-6 and IL-13 production in MC/9 cells and BMMCs.