Impaired D-myo-inositol 1,4,5-triphosphate generation from cord blood polymorphonuclear leukocytes.

D-myo-Inositol 1,4,5-triphosphate (IP3) is a key second messenger in many cells, including macrophages, T and B cells, and neutrophils, in which it regulates free intracellular calcium ion levels. In human polymorphonuclear leukocytes the rise of intracellular [Ca2+] is the signal that activates a number of functions such as adherence, aggregation, chemotaxis, and degranulation, which are typically depressed in newborn infants. IP3 generation can be stimulated by N-formyl-methionyl-leucylphenylalanine (fMLP) tripeptide, which mimics the naturally occurring bacterial oligopeptides. In this study both neonatal and adult polymorphonuclear leukocytes were stimulated by fMLP (1 x 10(-6) M) and the levels of IP3 were assayed by a specific radiometric method. The time course of IP3 generation was studied for up to 60 s in a total of 10 samples. The response appeared reduced in cord blood samples. To confirm this observation, we extended our study to a larger number of samples, quantitating [IP3] at the time peak of 10 s. As expected IP3 generation was significantly (F test, p < 0.0001, n = 39) lower in newborns than in adults (means +/- SD = 0.64 +/- 0.25; 1.26 +/- 0.36, ng/10(6) cells, respectively). Besides soluble stimulus, neutrophils were treated with a particulate stimulus, namely serum-treated zymosan, which is also able to stimulate IP3 synthesis from polymorphonuclear leukocytes. Serum-treated zymosan produced a prolonged elevation in the level of IP3, reaching a plateau within 120 s in both cord blood and in control samples.(ABSTRACT TRUNCATED AT 250 WORDS)