Research in Dr. Bloomquist's
laboratory centers on neuroimmune interactions which initiate
and perpetuate inflamatory responses, such as edema and smooth
muscle contraction, in the lung airways and in the gastrointestinal
tract. The long-term goal is to define the specific role of
sensory nerves in the development, amplification, dissemination,
and maintenance of inflammatory processes important in the
etiology of diseases such as asthma, chronic bronchitis, and
inflammatory bowel disease. The laboratory was the first to
show release of the tachykinin, substance P (SP), by a sulfidopeptide
leukotriene (leukotriene D4 , LTD4) in intestinal smooth muscle.
More recently we have shown the same interaction in guinea
pig airways. Additionally we have demonstrated leukotriene
dependent release of SP by another tachykinin, neurokinin
A. These studies have thus identified a major role for sulfidopeptide
leukotrienes not only as direct smooth muscle agonists but
as relay mediators which disseminate the inflammatory reponse
from the field of one sensory neuron to those of adjacent
sensory neurons, causing a spreading and amplifying local
release of sensory neuropeptides which are potent smooth muscle
agonists and mediators of edema. Using in situ hybridization
techniques, we have found that substance P is more highly
expressed in guinea pig than in rat sensory ganglia, in that,
in the guinea pig, SP, in addition to being expressed in small
nociceptive neurons, is also expressed in many large sensory
neurons of other sensory modalities.
We have recently shown expression
of precursor forms of SP in vagal tracheal and lung tissues
of the guinea pig. Localization of these precursor forms in
axons within the peripheral tissues indicates that complete
processing of SP from its larger peptide precursors occurs
during transport into the lungs and trachea and further suggests
a physiologic role for the precursors themselves.
Following sensitization with
subcutaneous ovalbumin we have demonstrated marked up regulation
of the NK1 class of tachykinin receptors especially in eosinophils
associated with the airways. |