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A J Coyle

Publications and source records attributed to A J Coyle.

62 records · Page 4Linked to original sources
PubMed1990

The requirement for platelets in allergen-induced late asthmatic airway obstruction. Eosinophil infiltration and heightened airway responsiveness in allergic rabbits.

In these studies, we have used an allergic rabbit model to investigate the role of platelets in the late asthmatic response (LAR) by depleting platelets with a guinea pig antirabbit platelet antiserum (APAS). Allergen exposure of immunized rabbits pretreated with normal guinea pig serum (NGPS) to serve as a control resulted in an early- and late-phase obstructive airway response that persisted for 6 h. When the immunized animals were pretreated with APAS, the magnitude of the LAR in terms of dynamic compliance was reduced by 86.2% (p less than 0.03), but there was no difference in the early response curve. Allergen challenge of animals treated with NGPS resulted in an increased bronchial responsiveness to inhaled histamine: PD50 Cdyn geometric mean +/- SEM before, 2.36 mg/ml (3.43-1.64); after, 0.60 mg/ml (0.67-0.54) (p less than 0.01). PD50 RL before, 1.78 mg/ml (2.4-1.32); after, 0.58 mg/ml (0.81-0.47) (p less than 0.05). In contrast, when animals were treated with APAS, there was a significant inhibition of allergen-induced airway hyperresponsiveness to inhaled histamine: PD50 Cdyn geometric mean +/- SEM before, 1.42 mg/ml (2.06-0.98); after, 1.10 mg/ml (1.41-0.86) (p less than 0.4). PD50 RL before, 1.62 mg/ml (2.22-1.39); after, 1.05 mg/ml (1.35-0.82) (p greater than 0.4). Analysis of bronchoalveolar lavage fluid revealed an increase in the number of neutrophils and eosinophils after allergen exposure in control animals (p less than 0.01). However, in animals rendered thrombocytopenic, the number of eosinophils, but not neutrophils, was significantly reduced (p less than 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)

Allergens↗
PubMed1989

Modification of allergen-induced airway obstruction and airway hyperresponsiveness in an allergic rabbit model by the selective platelet-activating factor antagonist, BN 52021.

Allergen challenge of eight ragweed-immunized rabbits elicited a prolonged airway obstruction that was evident during the 6-hour study period. Airway responsiveness to histamine was enhanced 24 hours after allergen exposure (geometric mean of the 50% reduction in effective dose [ED50] of dynamic compliance [Cdyn] before challenge, 3.46 mg/ml, decreased to 0.52 mg/ml after challenge, p less than 0.01; pulmonary resistance ED50 geometric mean before challenge, 3.50 mg/ml, decreased to 0.65 mg/ml after challenge, p less than 0.05). In a random crossover study, the selective platelet-activating factor antagonist, BN 52021 (60 mg/kg, orally, 1 hour before allergen challenge), significantly reduced the allergen-induced airway obstruction (p less than 0.005). In addition, pretreatment with BN 52021 reduced the associated increased airway responsiveness induced by allergen exposure (prechallenge Cdyn ED50, 1.93; after challenge, 2.13 mg/ml; pulmonary resistance ED50, 1.91 mg/ml before challenge and 1.69 mg/ml after challenge). These present observations suggest a role for platelet-activating factor in the pathogenesis of allergen-induced airway obstruction and in the development of airway hyperresponsiveness in an allergic rabbit model.

Airway Obstruction↗
PubMed1989

The role of platelet activating factor in allergic inflammation.

It is becoming increasingly apparent that platelet activating factor (PAF) is an important mediator in allergic disease. It is synthesized by a variety of cells including those which are thought to participate in the inflammatory process. In turn, PAF may stimulate these cells which further propagates the inflammatory process. Furthermore, PAF can mimic most of the characteristics which are relevant in allergic inflammation and PAF can produce effects comparable to that produced by antigen in animal models of allergic inflammation and in man. Other evidence to support the involvement of PAF in allergic disease has also arisen with the advent of PAF antagonists. Many PAF-induced responses can be attenuated by these agents and many antigen-induced responses in both animal models and in man can also be attenuated by PAF antagonists. This review attempts to summarize the results from studies which have investigated the role of PAF in allergic inflammation and the effects of PAF antagonists against both PAF and allergic-induced responses.

Animals↗
PubMed1989

The interaction between PAF, platelets and eosinophils in bronchial asthma.

Many mediators have been proposed to be important in the pathogenesis of bronchial asthma based solely on their ability to elicit airway smooth muscle contraction. However, such an approach fails to appreciate the underlying pathological changes as being central to the aetiology of the disease. Platelet activating factor (PAF) has been demonstrated to mimic many of the features of asthma including bronchial hyperreactivity, eosinophil recruitment, mucus secretion and smooth muscle hyperplasia. The recent availability of selective PAF antagonists has demonstrated the central role of PAF in allergic responses in experimental animals and at least in the skin of man. The precise mechanism by which PAF and antigen induce BHR is not completely understood but may involve an interaction between platelets and eosinophils. It is anticipated that further investigation into the relationship between PAF, platelets and eosinophils may provide a greater insight into the pathogenesis of the disease.

Asthma↗
PubMed1988

The effect of the selective PAF antagonist BN 52021 on PAF- and antigen-induced bronchial hyper-reactivity and eosinophil accumulation.

Sensitised guinea-pigs were exposed to an aerosol of ovalbumin (100-500 micrograms/ml) and normal animals were exposed to an aerosol of platelet activating factor (PAF) (250-1000 micrograms/ml). Twenty-four hours later, bronchial reactivity was assessed by measurement of air overflow in response to i.v. histamine or acetylcholine using the Konsett-Rossler technique. Additionally, bronchoalveolar lavage was performed by washing the lungs with 10 ml of 0.9% saline and differential counts obtained to assess the ability of PAF and antigen to elicit pulmonary inflammatory cell recruitment. Both PAF and antigen exposure produced a dose-related increase in bronchial reactivity, while treatment with the vehicle (either 0.25% bovine serum albumin or 0.9% saline) had no effect on airway responsiveness. Furthermore, both PAF and antigen exposure produced a selective accumulation of eosinophils into the airways. There was no significant change in the number of neutrophils, macrophages or lymphocytes. The selective PAF antagonist BN52021 inhibited both the development of bronchial hyper-reactivity and the eosinophil influx into the airways induced by PAF or antigen exposure. These observations suggest that PAF has a central role to play in the antigen induced eosinophil accumulation and subsequent bronchial hyper-reactivity.

Animals↗
PubMed1988

The effect of platelet-activating factor on histamine and muscarinic receptor function in guinea pig airways.

Platelet-activating factor (PAF) administered i.v. or by aerosol to guinea pigs elicited an increase in airway responsiveness to both acetylcholine and histamine when compared with guinea pigs exposed to the vehicle bovine serum albumin (BSA). After i.v. PAF, the ED100 for acetylcholine and histamine was 5.4 and 3.4 micrograms/kg, respectively, in comparison with 17 and 6 micrograms/kg, respectively, before PAF, representing approximately a 3- and 2-fold increase in responsiveness, respectively. After aerosol PAF (500 micrograms), the ED100 for acetylcholine and histamine was 13 and 7 micrograms/kg, respectively, whereas after aerosolized BSA, the ED100 for acetylcholine and histamine was 23 and 12 micrograms/kg, respectively, representing approximately a 2-fold increase in responsiveness. However, airway smooth muscle obtained from these PAF- or BSA-treated animals did not exhibit any differences in contractile response to histamine or acetylcholine in vitro. Likewise, there were not significant differences in the binding affinity or receptor density between PAF- and BSA-treated tissues with [3H]quinuclidinylbenzilate or [3H]pyrilamine binding, which were used to identify muscarinic and H1-histamine receptors, respectively. Furthermore, histamine and carbachol-induced phosphoinositide hydrolysis was similar in PAF- and BSA-treated tracheal smooth muscle preparations. Thus, PAF induces airway hyperresponsiveness in the guinea pig that is not related to changes in airway smooth muscle or to changes in muscarinic and histamine (H1) receptor density or function.

Acetylcholine↗
PubMedDate not supplied

The effect of the selective PAF antagonist WEB 2170 on PAF and antigen induced airway hyperresponsiveness and eosinophil infiltration.

Exposure of normal guinea pigs to an aerosol of PAF induced an increase in airway responsiveness to i.v. histamine, 24 h and 48 h post challenge compared to animals that received BSA alone. There was no significant alteration in airway responsiveness 1 h, 4 h or 72 h after PAF challenge. Exposure of actively sensitised guinea pigs to an aerosol of ovalbumin induced airway hyperresponsiveness to i.v. histamine, 24 h post challenge. PAF induced a selective increase in the percentage of eosinophils in bronchoalveolar lavage fluid 24 h after challenge, that persisted for at least 72 h post challenge. No significant increase in eosinophils was noted 1-4 h after PAF exposure. Antigen challenge of actively sensitised guinea pigs induced a significant increase in the percentage of eosinophils recovered in BAL fluid 24 h post challenge. Pretreatment of both normal and sensitised guinea pigs with the selective PAF antagonist WEB 2170 significantly inhibited both airway hyperresponsiveness and airway eosinophilia 24 h post challenge with aerosol PAF or allergen. These results further support the suggestion that PAF may play a central role in allergen induced eosinophil infiltration and airway hyperresponsiveness in the guinea pig.

Aerosols↗