Platelet-activating factor primes human eosinophil generation of superoxide

Area of Science:

• Immunology
• Pulmonary Medicine
• Cell Biology

Background:

• Platelet-activating factor (PAF) is a key inflammatory mediator implicated in airway obstruction and hyperresponsiveness.
• Pulmonary eosinophilia suggests a link between PAF and eosinophil involvement in airway inflammation.
• Direct PAF activation of eosinophils in vitro typically requires high, potentially unphysiologic concentrations.

Purpose of the Study:

• To investigate if low, physiologically relevant concentrations of PAF can prime eosinophils.
• To determine if primed eosinophils exhibit an enhanced response to subsequent stimulation by formylmethionylleucylphenylalanine (FMLP).
• To explore the cellular effects of low-dose PAF on eosinophils.

Main Methods:

• Eosinophils were preincubated with low PAF concentrations (1 x 10(-8) M and 1 x 10(-10) M) for short durations (1 and 15 min).
• Superoxide anion generation in response to FMLP stimulation was measured.
• Eosinophil density and CR3 receptor expression were assessed.
• Changes in cytosolic free Ca2+ concentrations were monitored.

Main Results:

• Short-term exposure to low PAF concentrations enhanced superoxide anion generation upon FMLP stimulation.
• Low PAF concentrations reduced eosinophil density and increased CR3 receptor expression.
• Nonactivating PAF concentrations induced transient increases in intracellular calcium.

Conclusions:

• Low concentrations of PAF transiently prime eosinophils, increasing their responsiveness to other stimuli.
• This priming effect involves changes in cell density, CR3 expression, and intracellular calcium.
• PAF-induced eosinophil priming may represent a mechanism for amplified inflammatory responses and airway injury.