Lack of neurokinin-1 receptor expression affects tissue mast cell numbers but not their spatial relationship with nerves.
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 (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 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 NK1-/- bone marrow. No differences in mast cell-nerve contact were observed. These results suggest that NK1 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 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(W)/Kit(W-v) mice with mast cells derived from different genetically engineered mice is a useful approach to further explore these mechanisms.
Drug Discovery, Johnson & Johnson Pharmaceutical Research and Development, Spring House, Pennsylvania, USA.
Michael R
MR
D'Andrea
Marcia R
MR
Saban
Norma P
NP
Gerard
Barry K
BK
Wershil
Ricardo
R
Saban
D000818:Animals; D016026:Bone Marrow Transplantation; D002452:Cell Count; D005260:Female; D015870:Gene Expression; D008407:Mast Cells / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000502:physiology*; D018040:Receptors, Neurokinin-1 / Q000378:metabolism*; D013270:Stomach / Q000033:anatomy & histology / Q000294:innervation; D001743:Urinary Bladder / Q000033:anatomy & histology / Q000294:innervation
D018040:Receptors, Neurokinin-1