The nuclei of human neutrophils typically consist of a linear array of three or 
four lobes joined by DNA-containing filaments. Terminal lobes are connected to 
internal lobes via a single filament, while internal lobes have two filaments, 
each to an adjacent lobe. Some lobes also have appendages of various shapes and 
sizes. In particular, up to 17% of neutrophil nuclei of healthy women exhibit a 
drumstick-shaped appendage that contains the inactive X chromosome. This report 
provides a detailed analysis of the relationship between nuclear morphology and 
the location of the X and Y chromosomes in human neutrophils. Fluorescent in 
situ hybridization analysis revealed that the X and the Y chromosomes of male 
neutrophil nuclei are randomly distributed among nuclear lobes. Similarly, in 
female neutrophil nuclei with a drumstick appendage, the active X chromosome is 
also randomly distributed among lobes. In contrast, the inactive X chromosome is 
preferentially located in a terminal lobe in over 90% nuclei with drumsticks. 
Within the terminal lobe of nuclei with drumsticks, the inactive X chromosome 
lies distal to the point of filament attachment in 80% of the nuclei. The 
inactive X chromosome also exhibits a specific orientation within the drumstick 
appendage, with over 95% of nuclei having the X centromere located toward the 
tip of the appendage. Female nuclei without a drumstick appendage also have one 
of the X chromosomes (presumably the inactive chromosome) preferentially 
situated in a terminal lobe. Nonrandom distribution of the inactive X chromosome 
is discussed in the context of a model that considers chromosomes as 
determinants of neutrophil nuclear morphology.