Topically Applied Nitric Oxide Induces T-Lymphocyte Infiltration in Human Skin, but Minimal Inflammation

Megan Mowbray, Xuejing Tan, Paul S. Wheatley, Adriano G. Rossi, Russell E. Morris, Richard B. Weller

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Nitric oxide (NO) plays an important role in the cutaneous response to
UV radiation and in cutaneous inflammation. The presence of inducible NO
synthase protein in a number of inflammatory dermatoses, coupled with
the induction of an intense cutaneous inflammatory infiltrate following
topical application of the NO donor-acidified nitrite (NO2),
has set the paradigm of NO being an inflammatory mediator in human
skin. Using zeolite NO (Ze–NO), a chemically inert, pure NO donor, we
have shown that NO per se produces little inflammation. Biologically, relevant doses of Ze–NO induce a dermal CD4-positive T-cell infiltrate and IFN-γ
secretion. In contrast acidified nitrite, releasing equal quantities of
NO (measured by dermal microdialysis and cutaneous erythema), induces
an intense epidermal infiltrate of macrophages with a similar dermal
infiltrate of CD3-, CD4-, CD8-, and CD68-positive cells and neutrophils.
Suction blisters were created in Ze–NO-treated and control skin. IFN-γ, but not IL-4, was detected in Ze–NO-treated skin (mean control 0.1±0.07pgmg−1 protein, mean IFN-γ 0.6±0.4pgmg−1 protein). We suggest that the potent inflammation induced by acidified NO2 is secondary to the release of additional mediators.

Original languageEnglish
Pages (from-to)352–360
Number of pages1
JournalJournal of Investigative Dermatology
Volume128
Issue number2
DOIs
Publication statusPublished - Feb 2008

Keywords / Materials (for Non-textual outputs)

  • iNOS, inducible NOS
  • NOS, NO synthases
  • NO, nitric oxide
  • NO2−, nitrite
  • Ze, zeolite
  • Ze–NO, zeolite–nitric oxide

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