Allergy or inflammation? From neuropeptide stimulation of human skin mast cells to studies on the mechanism of the late asthmatic response.
This short review examines two examples of studies into the mechanisms of allergic responses which have particular relevance to inflammation research. The first is the ability of human skin mast cells, but not those derived from lung, adenoids, tonsils or intestine, to release histamine in response to stimulation by neuropeptides including substance P, vasoactive intestinal polypeptide (VIP) and somatostatin. The neuropeptide activation site does not appear to be a classical tachykinin receptor but rather a binding site of low affinity and low specificity capable of interacting with neuropeptides and compounds with similar physicochemical characteristics. In contrast to IgE-dependent activation, neuropeptide stimulation of skin mast cells induces a rapid release of histamine with minimal generation of PGD2 and LTC4. This pseudo-allergic reaction is thought to underlie the weal and flare response in the skin and may have a role in urticaria. The second example describes studies to elucidate the mechanisms of the late asthmatic response by use of a guinea-pig model. As in man, both early and late phase responses in the guinea-pig are inhibited by sodium cromoglycate whereas only the early response is inhibited by the beta-adrenoceptor stimulant drug salbutamol. Examination of bronchoalveolar fluid has shown a temporal relationship between an airways neutrophilia and the late response. However, pharmacological manipulation and the use of an anti-neutrophil serum has shown that these events are not interdependent. The role of the airways eosinophilia requires further investigation.
Church
M K
MK
Immunopharmacology Group, Southampton General Hospital, UK.
Benyon
R C
RC
Lowman
M A
MA
Hutson
P A
PA
Holgate
S T
ST
D001249:Asthma / Q000209:etiology*; D003937:Diagnosis, Differential; D006801:Humans; D006967:Hypersensitivity / Q000175:diagnosis / Q000503:physiopathology*; D007249:Inflammation / Q000175:diagnosis / Q000503:physiopathology*; D008407:Mast Cells / Q000502:physiology; D009479:Neuropeptides / Q000502:physiology*
D009479:Neuropeptides