In:
The Journal of Immunology, The American Association of Immunologists, Vol. 170, No. 7 ( 2003-04-01), p. 3866-3873
Abstract:
Cutaneous neurogenic inflammation is a complex biological response of the host immune system to noxious stimuli. Present evidence suggests that zinc metalloproteases may play an important role in the regulation of neurogenic inflammation by controlling the local availability of neuropeptides, such as substance P (SP), that are capable of initiating or amplifying cutaneous inflammation after release from sensory nerves. To address the hypothesis that the dipeptidyl carboxypeptidase angiotensin-converting enzyme (ACE) is capable of modulating skin inflammation, we have analyzed murine allergic contact dermatitis (ACD) and irritant contact dermatitis (ICD) using wild-type C57BL/6J (ACE+/+) or genetically engineered mice with a heterozygous deletion of somatic ACE (ACE+/−). In 2,4-dinitro-1-fluorobenzene-sensitized ACE+/− mice, ACD was significantly augmented in comparison to ACE+/+ controls as determined by the degree of ear swelling after exposure to hapten. Likewise, systemic treatment of ACE+/+ mice with the ACE inhibitor captopril before sensitization or elicitation of ACD significantly augmented the ACD response. In contrast, local damage and neuropeptide depletion of sensory nerves following capsaicin, injection of a bradykinin B2, or a SP receptor antagonist before sensitization significantly inhibited the augmented effector phase of ACD in mice with functionally absent ACE. However, in contrast to ACD, the response to the irritant croton oil was not significantly altered in ACE+/− compared with ACE+/+ mice. Thus, ACE by degrading bradykinin and SP significantly controls cutaneous inflammatory responses to allergens but not to irritants, which may explain the frequently observed exacerbation of inflammatory skin disease in patients under medication with ACE inhibitors.
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.170.7.3866
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
2003
detail.hit.zdb_id:
1475085-5
