Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Allergic sheep respond to inhalation challenge with Ascaris suum antigen with an immediate bronchoconstriction that resolves within 2 to 4 h, followed by a second bronchial obstruction occurring 6.5 to 8 h after challenge. The purpose of this study was to determine if the antigen-induced late bronchial response in allergic sheep is mediator dependent and to determine the extent to which histamine and/or slow-reacting substance of anaphylaxis (SRS-A) are involved in this response. To do this, 10 conscious sheep with Ascaris suum hypersensitivity underwent an inhalation challenge with antigen, and the average increase in specific lung resistance (SRL = mean pulmonary flow resistance times thoracic gas volume) was determined for each animal between 6.5 and 8 h after challenge, i.e., the time of late bronchial response. On another occasion, separated by at least 14 days, the animals were rechallenged with antigen, but prior to the onset of the late response (5.5 h) the animals were treated with either the mast cell stabilizer cromolyn (1 mg/kg), the SRS-A antagonist FPL-55712 (3 ml of a 1% wt/vol solution), or the histamine H1. receptor antagonist chlorpheniramine (2 mg/kg). Compared with the control response, inhaled aerosols of cromolyn or FPL-55712 blocked the late increase in SRL (p less than 0.01). Intravenously administered chlorpheniramine alone, or in conjunction with atropine, had no effect on the late response. Finally, the late response was partially reversed by FPL-55712 inhalation. These results suggest that the late bronchial response after inhalation challenge in allergic sheep is mediator dependent, and that SRS-A is a principal mediator of this response.
 ...
PMID:The role of slow-reacting substance of anaphylaxis in the late bronchial response after antigen challenge in allergic sheep. 620 32

Tryptase, a mast cell serine protease, has been implicated in the pathophysiology of allergic asthma, but formal evidence to support this hypothesis has been limited by the lack of specific inhibitors for use in vivo. Therefore, in this study we examined the effects of two inhibitors of tryptase, APC 366 [N-(1-hydroxy-2-naphthoyl)-L-arginyl-L-prolinamide hydrochloride] and BABIM [bis(5-amidino-2-benzimidazolyl)methane] on antigen-induced early and late responses, airway responsiveness as measured by carbachol provocation, microvascular permeability as measured by bronchoalveolar lavage (BAL) albumin concentrations, and tissue eosinophilia from biopsies in allergic sheep. APC 366 and BABIM were administered by aerosol in all experiments. In vehicle control trials, antigen challenge resulted in peak early and late increases in specific lung resistance (SRL) of (mean +/- SE, n = 6) 259 +/- 30% and 183 +/- 27% over baseline, respectively. Treatment with APC 366 (9 mg/3 ml H2O given 0.5 h before, 4 h after, and 24 h after antigen challenge) slightly reduced the peak early response (194 +/- 41%), but significantly inhibited the late response (38 +/- 6%, p < 0.05 versus control trials). Twenty-four hours after challenge, APC 366 also completely blocked the antigen-induced airway hyperresponsiveness to inhaled carbachol observed in the control trial.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Tryptase inhibitors block allergen-induced airway and inflammatory responses in allergic sheep. 852 Jul 78

In preliminary studies we have observed that inhaled heparin blocks antigen-induced airway responses in sheep that develop only acute responses to inhaled antigen (acute responders), but not in sheep that develop both acute and later responses (dual responders). Because heparin is an antagonist of inositol triphosphate (IP3) (one of the pathways involved in stimulus-secretion-coupling in mast cells), the differential effect of inhaled heparin in acute responders and dual responders might indicate the involvement of different signaling pathways during IgE-mediated mast cell reactions. Therefore, in this study we compared the effects of heparin on antigen-induced bronchconstriction, allergic cutaneous reaction, and histamine release into bronchoalveolar lavage fluid (BAL) in sheep that develop only acute responses or dual responses to inhaled Ascaris suum antigen. Specific lung resistance (SRL) was measured in 21 sheep (eight acute responders; 13 dual responders) before and after inhalation challenge with antigen, without and after pretreatment with inhaled heparin (1,000 units/kg). Histamine in BAL was measured by RIA before and after segmental antigen challenge, without and after pretreatment with inhaled heparin (eight acute responders; eight dual responders). In acute responders, mean +/- SE SRL increased by 197 +/- 21% with antigen; this was prevented by inhaled heparin (deltaSRL = 15 +/- 7%; p < 0.05). In dual responders, inhaled heparin had no effect on antigen-induced early (deltaSRL = 328 +/- 51% versus 305 +/- 76%) or late (deltaSRL = 201 +/- 33% versus 163 +/- 15%) responses. After segmental antigen challenge, BAL mean +/- SE histamine increased from 2.09 +/- 0.8 nM to 75.4 +/- 21.1 nM in acute responders and 1.58 +/- 0.7 nM to 66.8 +/- 27.3 nM in dual responders (p < 0.01). Inhaled heparin inhibited the increase in BAL histamine by 81% in acute responders (p < 0.05) and by only 19% in dual responders (p = NS). As was seen in the airways, heparin attenuated the allergic cutaneous reaction in acute responders by 46% (p < 0.05), but it was ineffective in dual responders. In contrast, H-7, a nonspecific protein kinase C inhibitor, attenuated the cutaneous reaction in dual responders by 28% (p < 0.05), but it was ineffective in acute responders. These data suggest that heterogeneity of allergic airway response is related to difference in mast cell signal transduction; IP3 is the predominant second messenger in acute responders, whereas non-IP3 pathways may be involved in dual responders.
 ...
PMID:Heterogeneity of allergic airway responses in sheep: differences in signal transduction? 888 73