Role of mast cells in ion transport abnormalities associated with intestinal anaphylaxis: Correction of the diminished secretory response in genetically mast cell-deficient W/Wv mice by bone marrow transplantation

Mary H. Perdue*, Stephen Masson, Barry K. Wershil, Stephen J. Galli

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

139 Scopus citations

Abstract

To investigate the role of mast cells in transport abnormalities during intestinal anaphylaxis, we examined responses to antigen in isolated intestinal preparations from ovalbumin-sensitized genetically mast cell-deficient WBB6F1-W/Wv (W/Wv) mice and congenic normal WBBGF1-+/+ (+/+) mice. Changes in ion transport (primarily secretion of chloride ions) were indicated by increases in short-circuit current (Isc). In tissues from +/+ mice, antigen caused increases in Isc which were significantly inhibited by antagonists to histamine (diphenhydramine) and serotonin (ketanserin), by a cyclooxygenase inhibitor (piroxicam) and by a neurotoxin (tetrodotoxin). In preparations from W/Wv mice, antigen-stimulated responses were ∼ 30% of that in +/+ mice and were inhibited only by piroxicam. Responses to electrical transmural stimulation of nerves were ∼ 50% in W/Wv versus +/+ mice, and were inhibited by antagonists of mast cell mediators in +/+ but not W/Wv mice. Reconstitution of mast cells in W/Wv mice by intravenous injection of +/+ bone marrow cells restored the normal responses to both antigen and nerve stimulation. Our results indicate that mast cell-dependent mechanisms are primarily responsible for the ion secretion associated with intestinal anaphylaxis, but that other cells are also involved. In addition, our data provide evidence for the functional importance of bidirectional communication between nerves and mast cells in the regulation of ion transport in the gastrointestinal tract.

Original languageEnglish (US)
Pages (from-to)687-693
Number of pages7
JournalJournal of Clinical Investigation
Volume87
Issue number2
DOIs
StatePublished - 1991

Keywords

  • Hypersensitivity
  • Intestinal epithelium
  • Mast cells

ASJC Scopus subject areas

  • Medicine(all)

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