Supply and Release of Storage Neutrophils

Abstract

Depletion of the mature neutrophil reserve during bacterial sepsis is rare in adults but common in neonates; when it occurs, a fatal outcome is likely. Neutrophil reserve depletion was investigated in groups of premature, 1-day-old and 1-, 2-, and 4-week-old rats by measuring: (1) the size of the neutrophil storage pool, and (2) the proportion of this pool which was released from the storage compartment when a weight-standardized release stimulus was applied. It was found that the premature rat has a small neutrophil storage pool containing 1.28 ± 0.07 × 10⁶ cells/g body weight (x ± SE). This pool size increases to contain 4.35 ± 0.23 × 10⁶ cells/g in the 4-week-olds (p < 0.001). With a standard neutrophil storage pool release stimulus, the premature rats depleted 68 ± 4% of their neutrophil stores, vs. a depletion of only 13 ± 6% of the stores in the 4-week-olds (p < 0.001). The small neutrophil reserve and the exaggerated release of stored neutrophils in neonatal animals are factors which predispose neonates to neutrophil reserve exhaustion during bacterial sepsis.

Comparison of Pulmonary Neutrophils in the Adult and Neonatal Rat after Hyperoxia

“…Because neutrophil storage pools are lower in the neonate (31), it is conceivable that the bone marrow of neonates becomes depleted, and further neutrophils cannot be released into the circulation to migrate into the lung. Indeed, our findings that blood neutrophi1 counts did not increase to the same extent in neonates as adults after 0, exposure suggest that the neonates were unable to mount a circulating neutrophil response equivalent to the adult.…”

Decreased Stimulated GM-CSF Production and GM-CSF Gene Expression but Normal Numbers of GM-CSF Receptors in Human Term Newborns Compared with Adults

“…Specific differences in myelopoiesis have been demonstrated in term newborn rats compared with adult animals. Reduced neonatal rat myeloid progenitor pools, accelerated myeloid progenitor proliferative rates, and decreased total body neutrophil storage pools all predispose the newborn rat to depletion of mature effector neutrophils and a tendency to develop neutropenia during states of increased demand or overwhelming bacterial sepsis (2)(3)(4). During experimental sepsis (states of increased demand), adult animals increase their CFU-GM pool two to three times greater than baseline and increase their proliferative rate to approximately 75% of maximal capacity.…”

Effect of Recombinant Stem Cell Factor on Clonogenic Maturation and Cycle Status of Human Fetal Hematopoietic Progenitors

“…For instance, a n important problem in neonatology practice involves the very high incidence of nosocomial infections in extremely preterm infants (18). The basis for this defective antibacterial defense appears to involve a relatively small neutrophil reserve per kilogram of body weight (19,20), a significant limitation in up-regulating neutrophil production during bacterial infection (2 I), and relatively poor neutrophil adherence, chemotaxis, and superoxide generation (22)(23)(24)(25)(26)(27). Effective and safe methods of improving neutrophil production and function in preterm neonates would be of interest as potential means of decreasing the incidence or severity of infections.…”