The Chédiak-Higashi syndrome. Evidence that defective leukotaxis is primarily due to an impediment by giant granules

Abstract

The primary defect of the Chédiak-Higashi syndrome (CHS) which links the several known neutrophil abnormalities in this disorder remains enigmatic. In an attempt to clarify the mechanism of one of the abnormalities of CHS neutrophils, ie, chemotactic migration, the effect of filter pore size was examined in the standard Boyden chamber assay. The response of normal neutrophils to a gradient of zymosan-activated serum was not influenced by increasing the filter pore size from 5 to 8 microgram. However, while CHS neutrophils showed a significant reduction in migratory response from the controls with 5-mu filters, the difference was eliminated when 8-mu filters were employed. Again, when an arachidonic acid gradient was used as the stimulus, migration of CHS neutrophils through 8-mu filters equalled that of controls. These findings indicate the intact nature of the surface receptor and motility systems of the CHS neutrophils and further suggest that the previously defined chemotactic defect in these cells can be explained in terms of the mechanical impediment provided by the CHS giant cytoplasmic granules.