High-affinity
tyrosine kinase A (trkA)
neurotrophin receptors on neurons and nonneuronal cells elicit differentiation or survival functions in response to
nerve growth factor (
NGF), whereas the low-affinity
neurotrophin (p75) receptor modulates trkA activity or can independently cause apoptosis or NFkappaB-mediated survival functions. We examined dental tissues for the presence of trkA-like immunoreactivity (trkA-IR), to determine which nonneuronal cell types express it in normal compared with inflamed teeth and how the trkA-positive cells relate to those expressing the p75 receptor and/or
NGF. Normal and injured rat molars (dentin cavity for 4 h, 16-24 h, 3 days, 16 days, or 5 weeks) were immunoreacted using the ABC detection system for two anti-trkA
antibodies (sTA, Santa Cruz Biotechnology; rTA, L. Reichardt) and
antibodies against p75 and
NGF, all of which also stained pulpal nerve fibers. We report that, when using the sTA antibody (recognizing the intracellular carboxy terminal), nonneuronal trkA-IR was found in odontoblasts of normal teeth and also in invading polymorphonuclear leukocytes (PMNs) and reparative odontoblasts after injury. When using rTA (recognizing the extracellular domain of the receptor), nonneuronal trkA-IR was only found in odontoblasts. Odontoblasts also had
NGF-IR but did not label for
NGF mRNA. The lack of odontoblast
NGF mRNA suggests that
NGF is passed from fibroblasts to the adjacent odontoblasts, where it is picked up by receptor-mediated mechanisms for regulation of odontoblast function.
Tooth injury disrupts this system such that trkA-IR decreases in injured odontoblasts, p75 decreases in fibroblasts, and
NGF is upregulated by fibroblasts and accumulates in the injured pulp and surviving odontoblasts. Pulpal
NGF may contribute to chemoattraction for the invading leukocytes or their sTA-IR may have been induced in response to pulpal
NGF. Thus, tooth pulp has a different distribution of nonneuronal
NGF and its paracrine receptors during
inflammation compared with normal conditions.