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Am J Physiol Renal Physiol 283: F616-F629, 2002. First published May 22, 2002; doi:10.1152/ajprenal.00096.2002
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Vol. 283, Issue 4, F616-F629, October 2002

Mast cells mediate substance P-induced bladder inflammation through an NK1 receptor-independent mechanism

Ricardo Saban1, Norma P. Gerard2,3, Marcia R. Saban1, Ngoc-Bich Nguyen1, Douglas J. DeBoer4, and Barry K. Wershil5

1 Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73190; 2 Pulmonary Division, Beth Israel Deaconess Medical Center, and 3 Ina Sue Pelmutter Laboratory, Children's Hospital, Harvard Medical School, Boston, Massachusetts 02215; 4 Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, Wisconsin 53706; and 5 Department of Pediatrics, State University of New York, Health Science Center at Brooklyn, Brooklyn, New York 11203-2098

The role of neurokinin-1 receptors (NK1R) in the interaction between mast cells and substance P (SP) in bladder inflammation was determined. Mast cell-deficient KitW/KitW-v, congenic normal (+/+), and KitW/KitW-v mice that were reconstituted with bone marrow cells isolated from NK1R-/- mice were challenged by instillation of SP, antigen, or saline into the urinary bladder. Twenty-four hours after challenge, the bladders were prepared for morphological assessment and gene expression. SP-induced bladder inflammation was mast cell dependent and did not require NK1R expression on the mast cell. Cluster analysis identified functionally significant genes that were dependent on the presence of mast cells for their upregulation regardless of stimulus. Those include serine protein inhibitor 2.2, maspin, mitogen- and stress-activated protein kinase 2, and macrophage colony-stimulating factor 1. Our findings demonstrate that while mast cells are essential for both antigen- and SP-induced bladder inflammation, there are common genes and unique genes expressed in each type of inflammatory reaction. When combined with unique animal models, gene array analysis provides a useful approach for identifying and characterizing pathways involved in bladder inflammation.

transgenic/knockout; mast cells; inflammation; gene regulation; protein kinases/phosphatases


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