Ontogeny of the Immune System: Fetal Lamb as a Model

Raghunathan, Rukmani; Miller, Michael E.; Wuest, Carla J.; Faust, Judy

doi:10.1203/00006450-198405000-00012

Cited by 4 publications

(4 citation statements)

References 11 publications

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“…PMN were resuspended at 1 x lo6 PMNjml in RPMI-FCS. Ovine neutrophil chemotaxis was performed in acrylic blind-well chambers (Biorad, Richmond, CA) as previously described by us (9). Briefly, 0.2 x lo5 neutrophils in 0.2 ml were separated from the chemotactic factor or buffer by a 3 pm pore-size polycarbonate chemotactic filter.…”

Section: Methodsmentioning

confidence: 99%

“…Lymphocyte derived chemotactic factors have been demonstrated during in vitro allogeneic reactions (22) and in vivo in inb:red rats carrying heterozygous pregnancies (23). We have previously demonstrated a failure of N-LDCF production by mitogen-stimulated fetal mononuclear leukocyte (9). Fetal mononuclear leukocyte production of N-LDCF during alloreactior~s has not yet been thoroughly tested in this species.…”

Section: Neutrophil Chemotaxis Withmentioning

confidence: 99%

“…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.…”

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confidence: 99%

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Ontogeny of Neutrophil Chemotaxis in Fetal Lambs

et al. 1986

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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...

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Section: Methodsmentioning

confidence: 99%

Section: Neutrophil Chemotaxis Withmentioning

confidence: 99%

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Ontogeny of Neutrophil Chemotaxis in Fetal Lambs

et al. 1986

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“…In addition to the unique characteristics of the fetus itself as a recipient, there are several additional advantages of selecting sheep as an animal model: 1) sheep are fairly close in size to humans during development and throughout life, which should greatly facilitate, or even eliminate the need for, scale-up of the protocol for clinical human therapies once promising results have been obtained in the fetal sheep model, 2) the physiology and developmental processes are similar and therefore, sheep have been for decades the model to study normal fetal growth and fetal abnormalities [182][183][184][185], 3) in contrast to mice and rats, sheep are outbred, and thus present a diverse genetic background, just like humans, 4) the development of sheep immune system has been extensively studied and it closely parallels that of humans [186][187][188][189][190][191][192][193][194], 5) the long lifespan and large size allows the study of cellular fate in the same animal for several years after transplantation, which provides critical answers about long-term efficacy and safety of the therapy in question. Collectively, these properties make the fetal sheep an ideal model in which to test the therapeutic potential of MSC and obtain results that could readily be translated into clinical studies.…”

Section: The Fetal Sheep Modelmentioning

confidence: 99%