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PAF-dependent phosphatidylinositol turnover in platelets: differences between asthmatics and normal individuals
L H Block1, E Imhof, L R Emmons
1Department of Medicine, University of Basel, Switzerland.
Respiration; International Review of Thoracic Diseases
|January 1, 1990
Summary
Platelet-activating factor (PAF) inhalation affects airway conductance and circulation, increasing white blood cells but not platelet counts. Asthmatic patients show higher basal platelet IP3 and calcium levels, suggesting a role in asthma pathophysiology.
Area of Science:
- Pulmonary Medicine
- Cardiovascular Physiology
- Immunology
Background:
- Platelet-activating factor (PAF) is a potent mediator involved in inflammatory and allergic responses.
- Understanding PAF's effects on respiratory and cardiovascular systems, as well as platelet activation, is crucial for asthma research.
Purpose of the Study:
- To investigate the effects of inhaled platelet-activating factor (PAF) on pulmonary and cardiovascular systems.
- To examine PAF's impact on peripheral blood platelets in normal individuals and asthmatic patients.
- To explore the role of phosphatidylinositol (PI) turnover and intracellular calcium in PAF-induced platelet responses.
Main Methods:
- Inhalation challenge with nebulized PAF in normal subjects and asthmatic patients.
- Monitoring of pulmonary (specific airway conductance) and cardiovascular (heart rate, blood pressure) parameters.
- Analysis of peripheral blood cell counts (polymorphonuclear leukocytes, platelets).
- Measurement of phosphatidylinositol (PI) turnover, 1,4,5-inositoltrisphosphate (IP3) formation, and intracellular free calcium concentration ([Ca2+]i) in platelets.
Main Results:
- PAF inhalation caused decreased airway conductance and altered circulatory parameters (increased heart rate, decreased blood pressure).
- A transient increase in polymorphonuclear leukocytes was observed post-PAF inhalation.
- Basal levels of IP3 and [Ca2+]i were significantly higher in platelets from asthmatic patients compared to normal individuals.
- Platelets from both groups exhibited refractoriness to subsequent in vitro PAF exposure after inhalation challenge.
Conclusions:
- Inhaled PAF induces acute bronchoconstriction and cardiovascular changes, along with transient leukocytosis.
- Elevated basal IP3 and [Ca2+]i in asthmatic platelets suggest an altered platelet signaling pathway.
- PAF-induced platelet refractoriness may explain tachyphylaxis observed in normal and asthmatic individuals.