Mast cell-mediated changes in smooth muscle contractility during mouse giardiasis

Infect Immun. 2007 Sep;75(9):4514-8. doi: 10.1128/IAI.00596-07. Epub 2007 Jul 9.


Giardia intestinalis is a significant cause of diarrheal disease worldwide. Infections in animal models have been shown to cause changes in gastrointestinal transit that depend on adaptive immune responses and are mediated, in part, through neuronal nitric oxide synthase. Nitric oxide is an inhibitory neurotransmitter, and we therefore investigated potential excitatory pathways that might be involved in the response to Giardia infection. Infected mice exhibited increased spontaneous and cholecystokinin (CCK)-induced contractions of longitudinal smooth muscle. In contrast, enhanced contractile responses were not observed in response to acetylcholine, 5-hydroxytryptamine, or the protease-activated receptor-1 agonist peptide TFFLR. Giardia-induced changes in smooth muscle function appear to be mediated primarily by mast cells, as both spontaneous and CCK-induced contractions were blocked by pretreatment with either ketotifen or compound 48/80. Together, these data support a model in which CCK release triggers mast cell degranulation, leading to increases in smooth muscle contractility. These contractions, coupled with nitric oxide-mediated muscle relaxation, promote intestinal transit and parasite elimination.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Degranulation / physiology
  • Female
  • Giardia lamblia
  • Giardiasis / pathology*
  • Giardiasis / physiopathology
  • Mast Cells / metabolism
  • Mast Cells / parasitology
  • Mast Cells / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Muscle Contraction / physiology*
  • Muscle, Smooth / parasitology
  • Muscle, Smooth / pathology
  • Muscle, Smooth / physiology*