Neonatal Neutrophils Research Articles

Kinetics of phagocyte response to group B streptococcal infections in newborn rats.

To test the hypothesis that inadequate in vivo mobilization of leukocytes may contribute to the unique susceptibility of neonates to infection, we studied the kinetics of phagocyte response to neonatal and adult rats to intraperitoneal infection with group B streptococcus, type Ia. The 50% lethal dose was considerably greater for adults than for neonates (1.1 x 10(7) colony-forming units per g versus 2.7 x 10(2) colony-forming units per g). After challenge with group B streptococcus, type Ia, the number of neonatal peritoneal leukocytes increased more slowly than did those of adult rats. For example, at 4 h, the adult neutrophil count was 41 times greater than that of the neonate, but at 24 h, neonatal peritoneal neutrophils had not yet reached the adult 4-h level. Peritoneal macrophages also increased more rapidly in adults than in neonates. After intraperitoneal infection, both adults and neonates developed bacteremia, but adults cleared the bacteria with greater efficiency. Adult blood neutrophils increased 247% by 12 h and then decreased; neonatal neutrophils steadily decreased to a 57% reduction by 24 h. These data suggest that the neonatal neutrophil response to group B streptococcus, type Ia, infection is inadequate and may contribute to the high mortality associated with this infection.

Exhaustion of mature marrow neutrophils in neonates with sepsis

AN ADEQUATE SUPPLY of neutrophils is an important factor in host resistance to bacterial infection.' Indeed, when the supply is inadequate, the probability of surviving an infection diminishes. One sign of depleted neutrophil supply is blood neutropenia, a finding which is associated with increased mortality in infants with sepsis? 4 It is tempting to assume that the neutropenia of such infants is a reflection of inadequate neutrophil supply, but neutropenia can occur even when neutrophil supply is normal, as during the margination of circulating neutrophils primarily to post-capillary venular sites after endotoxin challenge? Thus, the finding of neutropenia itself does not establish that neutrophil supply is diminished, nor does it necessarily signify compromised host resistance. In order to determine whether neutropenia signaled neutrophil supply exhaustion in infected infants, we examined the marrow of nine living infants and six infants who had died from sepsis. In two infected neutropenic infants the neutrophil storage pool was found to be normal; both of these infants survived. Seven other neonates had diminished NSP, and those with the most profound depletion died. All infants who died of sepsis had NSP depletion. These observations suggest that neutropenia in infected infants frequently reflects NSP depletion. The identification of infants with NSP depletion may be of value as a prognostic sign and may aid in the consideration of therapeutic manuevers such as neutrophil transfusion.

Neutrophil chemiluminescence during the first month of life.

Postphagocytic chemiluminescence of neutrophils was evaluated in infants throughout the 1st month of life, in their mothers and healthy adults to investigate further the defective chemiluminescence of neonatal neutrophils described by earlier studies. Maternal and adult values were similar and served as controls. Abnormalities both of peak chemiluminescence and of the kinetics of light emission were detected in infant neutrophils throughout the 1st month of life. Infant responses were variable, particularly at birth, when neutrophils of some infants performed comparably to those of controls.

Bactericidal and Metabolic Function of Polymorphonuclear Leukocytes

The bactericidal and metabolic function of the phagocytic system requires integration of several complex humoral and cellular factors responding to different regulators. Polymorphonuclear leukocytes are highly mobile cells, capable of phagocytosis of bacteria or fungi with formation of a "cellular digestive system" containing reactive oxygen radicals, hydrogen ions, and digestive enzymes. The unique metabolism of oxygen in neutrophils results in release of energy as light (chemiluminescence) a response closely associated with microbiol killing. Neonatal neutrophils cope with normal bacterial challenges in vitro as efficiently as adult neutrophils; however, these cells have decreased capacity for locomotion, decreased deformability, decreased phagocytosis in low serum concentrations, and decreased chemiluminescence. These subtle defects in function can be amplified by exaggerated challenge which may be related to a higher incidence of sepsis during the neonatal period.

A Micromethod for Measuring Neutrophil Candidacidal Activity in Neonates

We developed a micromethod, requiring but a few drops of blood, for measuring the ability of neutrophils to kill ingested Candida albicans. The neutrophils of 10 normal adults killed 26.2 +/- 9.5% of ingested C. albicans in 2.5 hr in a standard fungicidal assay, and 21.4 +/- 6.5% in our new micromodification. Neutrophils from 14 full term, healthy 30- to 40-hr-old infants, studied with the micromethod, killed 23.2 +/- 6.0% of ingested C. albicans. We conclude that the neutrophils of normal neonates are competent in this sphere of antimicrobial activity.

Increased Reduction of Nitroblue Tetrazolium by Neutrophils of Newborn Infants

The spontaneous reduction of nitroblue tetrazolium (NBT) was found to be significantly elevated in phagocytes of normal newborn in fants in the absence of infection. This was evident using both a simple histochemical test and a more elalborate quantitative test for NBT reduction. During phagocytosis of latex particles, the expected rise in NBT reduction was significantly greater in neonatal phagocytes than in phagocytes of control subjects. The increased NBT reducing activity of neonatal neutrophils makes it impossible to use the NBT histochemical test for tile detection of bacterial infection in that age group. However, NBT-reduction tests can be used with profit in the neonatal period to diagnose chronic granulomatous disease when a positive family history warrants such an investigation. [See pdf for the Figure]