Fetal Neutrophils and Eosinophils Express Normal Levels of L-Selectin

Smith, Jeffrey B.; Tabsh, Khalil

doi:10.1203/00006450-199309000-00003

Cited by 37 publications

(19 citation statements)

References 16 publications

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“…Smith et al (23) reported that neutrophils from human preterm fetuses have expression of L-selectin similar to that of the adult. This would suggest that the developing infant is capable of producing L-selectin on the surface of its neutrophils.…”

Section: Discussionmentioning

confidence: 99%

Comparison of L-Selectin and CD11b on Neutrophils of Adults and Neonates during the First Month of Life

KIM

2003

Pediatric Research

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The newborn infant is particularly susceptible to infection in the first weeks of life and this may be, in part, related to functional impairment of neonatal neutrophils in regard to adherence, chemotaxis, and migration. Differences in expression of the neutrophil adherence molecules, L-selectin and CD11b/CD18 (Mac-1), have been previously demonstrated in cord blood and in very young infants (Յ 48 h) compared with adults, but it is unknown for how long these differences persist. We measured surface expression of neutrophil L-selectin and CD11b using flow cytometry in healthy term human newborns from 24 h through 4 wk of age. We also measured levels of soluble L-selectin using an ELISA in neonates though the age of 4 wk. Compared with adults, neonates expressed significantly less L-selectin on resting neutrophils through 4 wk of age, with the lowest levels being at 24 h. Expression of L-selectin on the neutrophil after activation with N-formyl-methionyl-leucyl-phenylalanine was less in the neonate than in the adult (p Ͻ 0.05) for the first week of life. Soluble L-selectin showed a steady increase with age in the neonates. Soluble L-selectin was significantly lower in the 24-h neonate compared with the adult and was higher in the 4-wk neonate compared with the adult. CD11b expression was similar between neonates and adults on unstimulated neutrophils, but upon activation, the neonatal neutrophil demonstrated significantly lower up-regulation of CD11b on the neutrophil surface through 4 wk of age compared with adults (p Ͻ 0.05 for all ages except 1 wk). These findings that differences in expression of L-selectin and CD11b from that in adults persist throughout the neonatal period provide further evidence that these differences may play a role in the neutrophil defects observed during the neonatal period. The newborn infant is particularly susceptible to severe bacterial and fungal infections (1, 2). It is unknown for how long this susceptibility persists, but it is a clinical practice to treat these infants as immunocompromised for at least the length of the neonatal period (first 28 d of life). Neonatal neutrophils, compared with those of adults, have been found to have functional impairments in their ability to adhere to an activated endothelial surface and to migrate in response to chemotaxins (2-6). These impairments may delay or prevent neutrophils from reaching inflammatory sites, thus inhibiting the ability of the neonate to effectively fight infection.Adherence of neutrophils to the vascular endothelium is an early step in the process of neutrophil migration into inflamed tissue and is mediated by proteins expressed on the surface of the neutrophil and the endothelium. Members of two important families of adhesion molecules located on the surface of the neutrophil are L-selectin and the ␤2-integrins. L-Selectin is found on neutrophils and other leukocytes and recognizes carbohydrate ligands on the endothelial cell, including sialyl Lewis (7). L-Selectin is thought to mediate, along with other selectin prote...

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Section: Discussionmentioning

confidence: 99%

Comparison of L-Selectin and CD11b on Neutrophils of Adults and Neonates during the First Month of Life

KIM

2003

Pediatric Research

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“…Subsequently, cells were incubated for 20 min at 4°C in the dark with MAbs against CD14, IL-6, IL-8, and tumor necrosis factor-␣ (TNF-␣; Pharmingen, Heidelberg, Germany). Preincubation with an excess of unlabeled anticytokine MAbs for 20 min at 4°C in the dark served as a negative control for intracellular staining to each sample (21). Monocytes were gated by means of their CD14 positivity, and number of cytokine-positive cells as well as the MFI were measured of a minimum of 2000 cells per sample.…”

Section: Methodsmentioning

confidence: 99%

“…In contrast, little is known to date about the phagocytic and oxidative capacity as well as the adhesion molecule expression of fetal neutrophils and monocytes. The expression of several adhesion molecules essentially involved in migration was reported to be significantly impaired in neonates and to contribute to the impaired neonatal immune response (18 -20); however, only very limited data are available for fetuses (21). Similarly, to our knowledge, there are no reports on the ability of fetal monocytes to produce proinflammatory cytokines in response to endotoxin challenge.…”

mentioning

confidence: 99%

Differential Maturation of the Innate Immune Response in Human Fetuses

et al. 2004

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Newborns and especially preterm infants show a unique susceptibility to severe bacterial infections that cause significant morbidity and mortality. As very few data are available on innate immune functions in human fetuses, we conducted a comprehensive study to investigate the expression of several adhesion molecules essentially involved in migration (CD11a, CD11b, CD11c, CD18, and CD62L). Furthermore, phagocytic activity, generation of respiratory burst products, and production of several proinflammatory cytokines were assessed. Various functions of the fetal innate immune system were demonstrated to be essentially different from those observed in term neonates or adults. Expression of several surface markers was significantly diminished on fetal granulocytes. Furthermore, a significantly reduced phagocytic activity of fetal granulocytes and monocytes was found, contrasted by an enhanced generation of reactive oxygen products. In addition, we demonstrate that significant numbers of fetal monocytes are capable of the production of proinflammatory cytokines in response to stimulation. However, the pattern of cytokine production is different from the more mature individuals: the number of IL-6 -and tumor necrosis factor-␣-positive monocytes were significantly diminished, whereas more IL-8 -producing monocytes were found compared with adults. The results of our study add significantly to our understanding of the maturation and impairment of the innate immune response. Neonates, especially preterm infants, are prone to severe and overwhelming bacterial infection with substantial morbidity and mortality. Despite intensive supportive care and early use of antibiotics, the rate of morbidity and mortality caused by infections remains high (1). Although multiple factors contribute to this susceptibility, the immaturity of the innate immune system, especially production of phagocytes and several phagocyte functions (e.g. chemotaxis, phagocytosis, respiratory burst, cytokine production) are of paramount importance (2,3). Evidence of this is provided by the pattern of infections closely resembling that seen in profound neutropenia (4). Depleted neutrophil storage pools and neutropenia were described to be associated with neonatal sepsis and are negative predictors of outcome (5,6). Several qualitative deficiencies of phagocyte function were demonstrated earlier in preterm infants and stressed or septic neonates. The functional deficiencies comprised migration, phagocytosis, and bactericidal potency, for example, release of bactericidal/permeabilityincreasing protein (7-15). However, normal or even enhanced spontaneous neutrophil respiratory burst activity in term and preterm neonates was reported in other studies (16,17). In contrast, little is known to date about the phagocytic and oxidative capacity as well as the adhesion molecule expression of fetal neutrophils and monocytes. The expression of several adhesion molecules essentially involved in migration was reported to be significantly impaired in neonates and to contri...

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“…A niunber of abnormalities have been described in the host defence mechanisms of the newborn infant, including neutrophil function. Studies of fetal and neonatal neutrophils (both term and premature) have consistently documented diminished chemotaxis [9][10][11][12][13] and adherence [14][15][16], deficiencies in the expression of adhesion molecules and complement receptors [17][18][19][20][21][22].…”

Section: C) 1995 Blackwell Sciencementioning

confidence: 99%

“…While Smith & Tabsh found that resting and stimulated fetal neutrophils express normal adult levels of L-selectin [21], Koenig et ai have suggested that there is less L-selectin loss from stimulated fetal cells [23]. The neutrophil expression of CDIla/CDI8 on term infant cells has been found to be no different from that on adult neutrophils [18].…”

Section: C) 1995 Blackwell Sciencementioning

confidence: 99%

Neutrophil adhesion molecules in term and premature infants: normal or enhanced leucocyte integrins but defective L-selectin expression and shedding

Rebuck

Gibson

Finn

1995

Clinical and Experimental Immunology

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SUMMARYThe functional deficits of neonatal neutrophils are well documented and are thought to contribute to the increased susceptibility of newborn infants to infection. We measured the adhesion molecules L-selectin. CDlla/CD18 and CDltb/CDI8 on neutrophils from the cord blood of term (n = 22) and premature (n = 32) infants using a whole blood method with flow cytometry and quantitative bead standards to enumerate cell surface receptors. We also assayed plasma for the shed form of L-selectin (sL-selectin). Our results suggested that L-selectin expression on term infant neutrophils is lower than that on adult neutrophils (unstimulated and stimulated, both P < 0 001). but that stimulated premature infant cells express higher L-selectin than term infants {P < 005); it is possible that this deficiency is caused by physiological changes occurring around the normal time of parturition. We observed reduced sL-selectin in term infants (P < OOOI) compared with adults, and even lower eoncentrations in premature infants (P < O-OOl). The sLselectin concentrations in plasma may be a refiection of granulopoiesis, which may be reduced in premature infants. Our results showed increased resting neonatal neutrophil expression of CDl lb/ CD18 compared with adults, and the absence of any neonatal deficit of the ability to up-regulate CDl lb/CD18 expression on stimulation. These findings are contrary to previous reports. Further studies suggested that the isolation procedures used in previous reports reduces the capability of the cells to respond to a formyl methionine leucine phenylalanine (fMLP) stimulus. This effect is more marked in neonatal neutrophils, suggesting that the previously reported deficiency is in fact due to the isolation techniques used rather than the cells" innate ability to up-regulale CDl lb/ CDI8 expression. The results of our study lead us to propose that the adhesive function of neonatal neutrophils may be less defective than previously thought.

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Fetal Neutrophils and Eosinophils Express Normal Levels of L-Selectin

Cited by 37 publications

References 16 publications

Comparison of L-Selectin and CD11b on Neutrophils of Adults and Neonates during the First Month of Life

Comparison of L-Selectin and CD11b on Neutrophils of Adults and Neonates during the First Month of Life

Differential Maturation of the Innate Immune Response in Human Fetuses

Neutrophil adhesion molecules in term and premature infants: normal or enhanced leucocyte integrins but defective L-selectin expression and shedding

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