The effects of neutrophil activation on migration

Lord, Ruth Anne Marie (1991) The effects of neutrophil activation on migration. University of Southampton, Doctoral Thesis.

Abstract

The aim of this study was to examine neutrophil locomotion following exposure to possible pre-activating stimuli. The objectives were (i) to validate suitable techniques for locomotion, (ii) to examine methods for leukocyte activation, and (iii) to determine whether leukocyte activation affects locomotion.

Test stimulants were shown to induce various neutrophil functions in an incubation procedure which activated the cells without affecting viability. Migration of pre-activated cells was assessed using a modified raft technique under standardised assay conditions.

In vitro pre-activation, resulted in a dose-dependent, non-preferential and significant (p< 0.001) reduction in migration. This loss of locomotion was not associated with humoural factors, but was cell-based, supporting the concept that activated cells operating in situ are not excited to move. This loss of locomotory capacity may be associated with enhancement of other neutrophil functions. Thus, activation of one neutrophil function appears to modulate the other functions. Random migration was only affected after high dose pre-activation and was restored following washing. Morphological studies showed a marked increase in microfilamentous structures associated with neutrophil activation while pharmacological studies implicated the involvement of microtubules, calcium ions, calmodulin and the cell membrane in deactivation. Taken together, these results suggest that deactivation inhibits the cells' migratory machinery.

Ex vivo studies showed that neutrophil function was significantly impaired in both surgery and hayfever patients. In both groups this was associated with in vivo neutrophil activation. There was evidence of deactivation in surgical patients as a result of induction of the alternative complement pathway. However, the alteration in neutrophil function in rhinitic patients was associated with an increase in sensitivity to stimulation.

This record has no associated files available for download.

Contributors

Download statistics