PAF-acether and experimental anaphylaxis as a model for asthma.
Several lines of evidence indicate that platelet-activating factor (PAF-acether) is implicated in hypersensitivity reactions. Indeed, PAF-acether reproduces the features of asthma in vivo and in vitro, since it induces bronchoconstriction, hypotension, and hemoconcentration and activates platelets and leukocytes. Both PAF-acether and antigen evoke eosinophil margination and diapedesis in guinea pig lung parenchyma and bronchial submucosa. Furthermore, intradermal administration of PAF-acether to atopics induces a more intense eosinophil degranulation as compared to normal subjects. PAF-acether also induces bronchopulmonary hyperresponsiveness in various animal models and in humans. We showed that lungs from actively sensitized guinea pigs exhibit an in vitro bronchopulmonary hyperresponsiveness to PAF-acether as compared to nonsensitized animals. This phenomenon is probably due to a lung invasion by inflammatory cells or to a variation of the reactivity of resident lung cells such as alveolar macrophages. In these cells, the cyclic adenosine monophosphate content is much less increased by prostaglandin E2 and salbutamol when they are obtained from actively sensitized animals.
Pretolani
M
M
Unité de Pharmacologie Cellulaire, Unité Associée Institut Pasteur/INSERM No. 285, Paris, France.
Lellouch-Tubiana
A
A
Lefort
J
J
Bachelet
M
M
Vargaftig
B B
BB
D000707:Anaphylaxis / Q000503:physiopathology*; D000818:Animals; D001249:Asthma / Q000503:physiopathology*; D004804:Eosinophils / Q000502:physiology; D006168:Guinea Pigs; D015289:Leukotrienes / Q000502:physiology; D008168:Lung / Q000473:pathology / Q000503:physiopathology; D008264:Macrophages / Q000502:physiology; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000502:physiology*; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface / Q000502:physiology; D043562:Receptors, G-Protein-Coupled
D015289:Leukotrienes; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor