Effect of Platelet Activating Factor with and without Receptor Antagonist (WEB2170) on Morphology of Isolated Cochlear Outer Hair Cells

Abstract

Platelet activating factor (PAF), generated from biologically active phospholipids, has been implicated as a potent inflammatory mediator and has been shown to be involved in many pathological processes, especially in inflammation and allergy. It has been suspected that PAF may be one of the inflammatory mediators in middle ear effusion that can induce sensorineural hearing loss, as observed in chronic otitis media. The PAF receptor antagonist WEB2170 has been studied extensively, and its inhibitory effects against various PAF actions are well proven in otologic systems. The purpose of our study was to determine the effect of superfusion of PAF and WEB2170 on morphological changes in isolated cochlear outer hair cells (OHCs). Isolated OHCs from adult chinchilla cochleas were exposed to albumin-phosphate-buffered saline solution (1 mg/mL), WEB2170 (5 mg/30 mL), PAF (1 μmol/L), or both PAF (1 μmol/L) and WEB2170 (5 mg/30 mL). All experiments were performed at an osmolality of 305 ± 5 mOsm at room temperature for 30 minutes. The cells were observed with an inverted microscope; the images were stored and analyzed on the Image Pro-Plus program. The OHCs exposed to control albumin-phosphate-buffered saline solution or to WEB2170 did not show any significant change in cell shape or length. The cells exposed to 1 μmol/L of PAF showed ballooning and significant shortening of the mean cell length in 15 to 20 minutes. These morphological changes in OHCs can be prevented by pretreating OHCs with WEB2170. This study demonstrated that exposure to PAF causes morphological changes in isolated OHCs that can be prevented by the PAF receptor antagonist WEB2170.