Lack of neurokinin-1 receptor expression affects tissue mast cell numbers but not their spatial relationship with nerves

1 Drug Discovery, Johnson & Johnson Pharmaceutical Research and Development, Spring House, Pennsylvania; 2 Department of Physiology, The Oklahoma University Health Sciences Center, Oklahoma City, Oklahoma; 3 Pulmonary Division, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts; 4 Ina Sue Pelmutter Laboratory, Children's Hospital, Harvard Medical School, Boston, Massachusetts; and 5 Department of Pediatrics, The Children's Hospital at Montefiore and Albert Einstein College of Medicine, Bronx, New York Submitted 8 July 2004 ; accepted in final form 24 September 2004 A spatial association between mast cells and nerves has been described in both the gastrointestinal and genitourinary tracts. However, the factors that influence the anatomic relationship between mast cells and nerves have not been completely defined. It has been suggested that the high-affinity receptor for substance P [neurokinin-1 (NK 1 )] might modulate this interaction. We therefore assessed mast cell-nerve relationships in tissues isolated from wild-type and NK 1 receptor knockout (NK 1 –/– ) mice. We now report that, in the complete absence of NK 1 receptor expression, there is a significant increase in the number of mast cells without a change in the anatomic 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, number, and contact with nerve elements. For this purpose, mast cell-deficient Kit W /Kit W–v mice were reconstituted with wild-type or NK 1 –/– bone marrow. No differences in mast cell-nerve contact were observed. These results suggest that NK 1 receptor expression is important in the regulation of the number of mast cells but is not important in the interaction between mast cells and nerves. Furthermore, the interaction between mast cells and nerves is not mediated through NK 1 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 W /Kit W–v mice with mast cells derived from different genetically engineered mice is a useful approach to further explore these mechanisms. cystitis; substance P; disease animal model Address for reprint requests and other correspondence: R. Saban, Dept. of Physiology, College of Medicine, Univ. of Oklahoma Health Sciences C