Development of chemotactic factor inactivation - a fetal lamb model.

Abstract

Summary: To study the developmental pattern of chemotactic factor in-activator (CFI) activity, although avoiding the effects of labor and delivery, serial blood samples were obtained from eight chronically catheterized lamb fetuses, 13 pregnant, and 13 nonpregnant ewes. The biologic profiles of adult sheep neutrophils in response to sheep C5-derived chemotactic fractions (C5-fr) were determined by the chemotactic and lysosomal enzyme release assays. CFI activity in sheep plasma was characterized and measured by the % inhibition of C5-fr-induced neutrophil lysosomal enzyme release. The chemotactic and enzyme release profiles of sheep neutrophils paralleled those of human neutrophils. Sheep plasma was shown to contain a CFI-like activity similar to that in human plasma. Mean CFI activity was higher in the plasma of pregnant ewes as compare to nonpregnant ewes (7.60 versus 5.15%, P < 0.001). Higher CFI levels (39.5%) were shown in the plasma of chronically catheterized fetuses early in the third trimester of pregnancy (109 days gestational age). These fetal levels decreased progressively to attain normal adult levels at fetal maturity (147 days gestational age) and no significant changes were noted at or after birth. Because identical changes occurred in all chronically catheterized fetuses, a developmental pattern was defined for CFI. Control CFI levels from six acutely catheterized fetuses did not differ from those predicted by the developmental pattern. Thus, the changes in CFI activity were not related to the chronic catheterization or to events surrounding labor and delivery; rather CFI levels correlated best with fetal immaturity. CFI levels correlated inversely with ability of zymosan activated plasma to induce neutrophil chemotaxis (r = —0.96, P < 0.01), suggesting that CFI plays a major role in the regulation of leukocytes chemotaxis. These data confirm previous findings in human neonates and provide a model for future studies. Further studies into the biology of the changes in CFI activity in the fetus and the influence of such high risk factors as prematurity, fetal distress or premature rupture of membranes should enhance our understanding of the immunocompromised neonate.