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Infection and Immunity, September 2007, p. 4514-4518, Vol. 75, No. 9
0019-9567/07/$08.00+0     doi:10.1128/IAI.00596-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Mast Cell-Mediated Changes in Smooth Muscle Contractility during Mouse Giardiasis{triangledown}

Erqiu Li,1,{dagger} Aiping Zhao,2,{dagger} Terez Shea-Donohue,2 and Steven M. Singer1*

Department of Biology, Reiss Science Building, Room 406, Georgetown University, Washington, DC 20057,1 Mucosal Biology Research Center, University of Maryland Medical Center, Baltimore, Maryland 212012

Received 25 April 2007/ Returned for modification 30 May 2007/ Accepted 30 June 2007

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.

* Corresponding author. Mailing address: Department of Biology, Reiss Building, Room 406, Georgetown University, Washington, DC 20057. Phone: (202) 687-9884. Fax: (202) 687-5662. E-mail: sms3{at}georgetown.edu

{triangledown} Published ahead of print on 9 July 2007.

Editor: W. A. Petri, Jr.

{dagger} Both authors contributed equally to this work.

Infection and Immunity, September 2007, p. 4514-4518, Vol. 75, No. 9
0019-9567/07/$08.00+0     doi:10.1128/IAI.00596-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.





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