Effect of activators and the phosphodiesterase inhibitors Pentoxifylline and Enoximone on the deformability of neutrophils in neonates and adults

Abstract

Stimulated polymorphonuclear leukocytes (PMN) are extremely rigid compared to resting PMN. They may obstruct narrow vessels and contribute to ischaemic organ injury. Deformability is a prerequisite for both active and passive movement in the microcirculation. The investigation was designed to study whether stimulators and inhibitors of stimulation show different effects on deformability of neonatal and adult PMN. Deformability of PMN was assessed by complete aspiration of a PMN into a micropipette with an internal diameter of 5 microm. Blood samples from 20 neonates and 20 adults were studied before and after stimulation with N-formyl-methionyl-leucyl-phenylalanine (fMLP), interleukin-8 (IL-8) or tumour necrosis factor-alpha (TNF-alpha). Moreover, effects of the phosphodiesterase inhibitors Pentoxifylline (PTX) and Enoximone on the deformability of stimulated PMN were investigated. fMLP, IL-8 and TNF-alpha significantly delayed aspiration times of PMN in relation to the concentrations of the stimulators. The addition of PTX or Enoximone to stimulated PMN increased the deformability up to 60% depending on the concentration of the inhibitors. No significant differences in the aspiration times were found between neonatal and adult PMN at any of the experimental conditions after activation with the three stimulators and treatment with the two inhibitors. Neonatal and adult PMN show similar reduction of passive deformability when stimulated with either fMLP, IL-8 or TNF-alpha compared to resting PMN and a similar improvement of deformability in response to PTX or Enoximone.