PAF-induced bronchial hyperresponsiveness in the rabbit: contribution of platelets and airway smooth muscle.

نویسندگان

  • A J Coyle
  • D Spina
  • C P Page
چکیده

1. Aerosol administration of platelet activating factor (PAF) to normal rabbits induced an enhanced airway responsiveness to inhaled histamine, 6 and 24 h after exposure. Following exposure to bovine serum albumin (BSA) as the carrier molecule for PAF, there was an increase in airway responsiveness to histamine 6 h after challenge, although by 24 h this was not significantly different from the responsiveness of airways to histamine before BSA. 2. PAF-induced bronchial hyperresponsiveness at 24 h was associated with a substantial increase in the number of neutrophils and mononuclear cells and a small, but significant increase in the number of eosinophils in the lungs as assessed by bronchoalveolar lavage. BSA exposure failed to alter the total number of cells in the lungs, although there was a significant increase in the number of neutrophils in the bronchoalveolar lavage fluid. 3. Selective platelet depletion with a guinea-pig anti-rabbit platelet serum inhibited PAF-induced bronchial hyperresponsiveness. In addition, there was an attenuation of PAF-induced airway inflammation in animals rendered thrombocytopenic. 4. The contractile potency to histamine, methacholine and carbachol was similar in intrapulmonary bronchi taken from rabbits exposed to an aerosol of BSA or PAF. Furthermore, the relaxant potency to the non-selective beta-adrenoceptor agonist isoprenaline, was unaltered in PAF-treated rabbits. In contrast, there was a 2.58 fold reduction in the relaxant potency to theophylline in rabbits exposed to PAF compared with rabbits exposed to BSA. 5. These results suggest that in the rabbit, PAF-induced bronchial hyperresponsiveness at 24 h is associated with airways inflammation and is dependent upon platelet activation, but is not related to changes in airway smooth muscle function.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

The role of RhoA-mediated Ca2+ sensitization of bronchial smooth muscle contraction in airway hyperresponsiveness.

Smooth muscle contraction is mediated by Ca2+-dependent and Ca2+-independent pathways. The latter Ca2+-independent pathway, termed Ca2+ sensitization, is mainly regulated by a monomeric GTP binding protein RhoA and its downstream target Rho-kinase. Recent studies suggest a possible involvement of augmented RhoA/Rho-kinase signaling in the elevated smooth muscle contraction in several human dise...

متن کامل

The action of platelet activating factor and its antagonism by WEB 2086 on human isolated airways.

This study investigated the direct and indirect effects of platelet activating factor (PAF, PAF-acether) on human isolated airways. PAF caused a single non-repeatable contraction which was found to be variable both between lung samples and within tissues from the same lung. The range of contractions induced by PAF, 7 X 10(-8), M and 7 X 10(-7) M was 2-55% and 3-72% of the maximal response to ca...

متن کامل

Is platelet activating factor (PAF) an important mediator in bronchial asthma?

The development of selective PAF receptor antagonists may provide a novel approach to the treatment of human bronchial asthma. In preclinical animal models of human asthma, PAF receptor antagonists have been found to be efficacious in blocking antigen-induced changes in lung function. However, the majority of these models involve acute inflammatory events and transient changes in lung function ...

متن کامل

An endothelin receptor antagonist, SB-217242, inhibits airway hyperresponsiveness in allergic mice.

Within the airways, endothelin-1 (ET-1) can exert a range of prominent effects, including airway smooth muscle contraction, bronchial obstruction, airway wall edema, and airway remodeling. ET-1 also possesses proinflammatory properties and contributes to the late-phase response in allergic airways. However, there is no direct evidence for the contribution of endogenous ET-1 to airway hyperrespo...

متن کامل

Decreased airway narrowing and smooth muscle contraction in hyperresponsive pigs.

Increased smooth muscle contractility or reduced smooth muscle mechanical loads could account for the excessive airway narrowing and hyperresponsiveness seen in asthma. These mechanisms were investigated by using an allergen-induced porcine model of airway hyperresponsiveness. Airway narrowing to electric field stimulation was measured in isolated bronchial segments, over a range of transmural ...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • British journal of pharmacology

دوره 101 1  شماره 

صفحات  -

تاریخ انتشار 1990