Submitted on July 8, 2004
Accepted on September 24, 2004
Lack of neurokinin 1 receptor expression effects tissue mast cell numbers but not their spatial relationship with nerves
Michael R D'Andrea1, Marcia R Saban2, Norma P Gerard3, Barry K Wershil4, and Ricardo Saban2*
1 Drug Discovery, Johnson & Johnson Pharmaceutical Research and Development, Spring House, PA, USA
2 Department of Physiology, The University Oklahoma Health Sciences Center, Oklahoma City, OK, USA
3 Pulmonary Division, Beth Israel Deaconess, Harvard Medical School, Boston, MA, USA; Ina Sue Pelmutter Laboratory, Children's Hospital, Harvard Medical School, Boston, MA, USA
4 Department of Pediatrics, The Children's Hospital at Montefiore and Albert Einstein College of Medicine, Bronx, NY, USA
* To whom correspondence should be addressed. E-mail: ricardo-saban{at}ouhsc.edu.
A spatial association between mast cells and nerves has been described in both the gastrointestinal and genitourinary tracts. However, the factors that influence the anatomical relationship between mast cells and nerves have not been completely defined. It has been suggested that the high affinity receptor for substance P (NK1)might modulate this interaction. We therefore assessed mast cell-nerve relationships in tissues isolated from wild type and NK1 receptor knockout (NK1-/-)mice. We now report that in the complete absence of NK1 receptor expression there is a significant increase in the number of mast without a change in the anatomical relationship between mast cell and nerves in stomach and bladder tissues at the light microscopic level. We next determined whether transplanted mast cells would maintain their spatial distribution, numbers, and contact with nerves elements. For this purpose, mast cell-deficient KitW/KitW-v mice were reconstituted with wild type (+/+) or NK1-/- bone marrow. No differences in mast cell - nerve contact were observed. These results suggest that NK1 receptor expression is important in regulating the number of mast cells, but not the interaction between mast cells and nerves. Furthermore, the interaction between mast cells and nerves is not mediated through NK1 receptor expression on the mast cell. Further studies are needed to determine the molecular pathway involved in mast cell migration and interaction with nerve elements, but the model of reconstitution of Kit mice with mast cells derived from different genetically-engineered mice is a useful approach to further explore these mechanisms.
