Ontogeny of Neutrophil Chemotaxis in Fetal Lambs

Abstract

ABSTRAfl. Ontogeny of neutrophil chemotactic response using endotoxin activated adult sheep plasma as a source of complement derived chemotactic factor was examined in fetal lambs of gestational age 120-150 days. (Gestational period in sheep is approximately 150 days.) Neutrophils from fetal lambs of gestational age 120-130 days failed to respond to this chemotactic factor whereas neutrophils from fetal lambs above 131 days of gestational age responded at levels comparable to adult values. Examination of neutrophil chemotaxis in older fetuses using a different chemotactic factor derived from mitogen stimulated adult mononuclear cells revealed a selective failure of fetal neutrophils to respond to lymphocyte-derived chemotactic factor in the presence of a normal response to complement derived chemotactic factor. Among prematurely delivered twin fetuses alterations in comparison with the first twin or age-matched controls in peripheral neutrophi1 count (increase) and in chemotaxis (increase or decrease) were noted in second of twins delivered r 20 min after the first lamb, suggesting an extreme sensitivity of neutrophil functions to a variety of influences, similar to that seen in humans. Directed migration or chemotaxis of phagocytes induced by various chemotactic agents is an essential component of inflammatory response. Defects in chemotaxis are associated, as a clinical consequence, with an increased susceptibility to infections. Defects in phagocyte chemotaxis may be due to membrane defects, reduced number of receptors for the chemotactic agent, or to cytoskeletal abnormalities. The chemotactic defect of human neonatal phagocyte originally described by Miller (1) may be due to deficiencies in any or all these components (2-5). Ontogeny of some phagocytic functions, but not chemotaxis, has been evaluated in fetal and neonatal animal models (6, 7). The ovine fetus has been shown by us and other investigators to be an appropriate animal model to study the ontogeny of various biological phenomena (8,9). In this report, we describe the developmental sequence of neutrophil chemotaxis in fetal lambs, utilizing EAP as a source of complement-derived chemotactic factor. Results from simultaneous evaluation of neutrophil chemotactic responses to EAP and another chemotactic factor derived from mitogen-stimulated adult ovine mononuclear leukocyte (N-LDCF) in a limited number of fetuses are presented. In addition, neutrophil counts and chemotaxis in normal fetal lambs and their twins have been compared to document alterations that may be due to "stress" of delayed delivery. MATERIALS AND METHODSSample collection. Normal adult sheep were used as controls.Heparinized (10 U/ml) blood was collected from the external jugular vein. Lambs of gestational age 120-1 50 days and postnatal age 1-6 days were compared with adults. The gestational age was determined by time-dated breeding. The fetal lambs were normal and were being delivered prematurely for other studies. The fetuses were exposed by hysterotomy under maternal spinal anes...

Staphylococcus-associated Abortions in Ewes with Long-term Central Venous Catheterization

“…Although bacteria were seen in all lungs from which C-pS were isolated, neutrophils were seen only in the lungs of older fetuses (from 114 DOG onward). Mature neutrophils and complement activity are reported to appear in ovine fetal blood at approximately 123 DOG, 8,19,25 and neutrophil chemotaxis to endotoxin is reported to reach adult levels by 131 DOG. 19 It was presumed that pulmonary inflammation occurred in the infected fetuses only after adequate maturation of the fetal nonimmune defense systems.…”