Neutrophil and endothelial adhesive function during human fetal ontogeny
Open accessAbstract
Leukocyte recruitment is ontogenetically regulated during fetal life, with strongly impaired adhesiveness of fetal leukocytes and endothelial cells, during early fetal development. Attenuation of the immune response contributes to the high rate of neonatal infections, particularly in premature infants. Whereas our knowledge of innate immune functions in mature neonates is growing, little is known about the ontogeny of neutrophil recruitment. We investigated neutrophils and ECs in the course of gestation with respect to rolling and adhesive functions. With the use of microflow chambers, we demonstrate that the neutrophilˈs ability to roll and adhere directly correlates with gestational age. These adhesion-related abilities are very rare in extremely premature infants (<30 weeks of gestation), which may correlate with our observation of markedly reduced expression of PSGL-1 and Mac-1 on neutrophils in preterm infants. In parallel, the capacity of HUVECs to mediate neutrophil adhesion under flow increases with gestational age. In addition, HUVECs from extremely premature infants exerting the lowest ability to recruit adult neutrophils show a diminished up-regulation of E-selectin and ICAM-1. Finally, by following neutrophil function postnatally, we show that maturation of PMN recruitment proceeds equivalently during extra- and intrauterine development. Thus, PMN recruitment and EC adhesion-related functions are ontogenetically regulated in the fetus, which might contribute significantly to the high risk of life-threatening infections in premature infants.
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The function of all components of innate immunity is weak in newborns compared with later life.
“These cells develop and mature during fetal life, but at different times, and the function of all components of innate immunity is weak in newborns compared with later life.”
From Evolution of the immune system in humans from infancy to old age (2015) · cites this paper as [3]
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Cites
Jaffe, E. A., Nachman, R., Becker, C. G., & Minick, C. (1973) · Journal of Clinical Investigation · doi:10.1172/jci107470 · Cited by 7,146 · see citing works
Getting to the site of inflammation: the leukocyte adhesion cascade updated
Ley, K., Laudanna, C., Cybulsky, M. I., & Nourshargh, S. (2007) · Nature Reviews Immunology · doi:10.1038/nri2156 · Cited by 4,354 · see citing works
Liggins, G. C., & Howie, R. N. (1972) · Pediatrics · doi:10.1542/peds.50.4.515 · Cited by 2,544 · see citing works
Stoll, B. J., Hansen, N. I., Fanaroff, A. A., Wright, L. L., Carlo, W. A., Ehrenkranz, R. A., Lemons, J. A., Donovan, E. F., Stark, A. R., Tyson, J. E., et al. (2002) · PEDIATRICS · doi:10.1542/peds.110.2.285 · Cited by 2,349 · see citing works
Lawrence, M. B., & Springer, T. A. (1991) · Cell · doi:10.1016/0092-8674(91)90393-d · Cited by 2,157 · see citing works
Innate immunity of the newborn: basic mechanisms and clinical correlates
Levy, O. (2007) · Nature reviews. Immunology · doi:10.1038/nri2075 · Cited by 1,227 · see citing works
Trends in neonatal morbidity and mortality for very low birthweight infants
Fanaroff, A. A., Stoll, B. J., Wright, L. L., Carlo, W. A., Ehrenkranz, R. A., Stark, A. R., Bauer, C. R., Donovan, E. F., Korones, S. B., Laptook, A. R., et al. (2007) · American Journal of Obstetrics and Gynecology · doi:10.1016/j.ajog.2006.09.014 · Cited by 1,097 · see citing works
Trends in Neonatal Morbidity and Mortality for Very Low Birthweight Infants
(2007) · Obstetric Anesthesia Digest · doi:10.1097/01.aoa.0000288247.39620.5a · Cited by 931 · see citing works
Cronstein, B. N., Kimmel, S. C., Levin, R. I., Martiniuk, F. T., & Weissmann, G. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.21.9991 · Cited by 725 · see citing works
Estimating the causes of 4 million neonatal deaths in the year 2000
Lawn, J. E., Wilczynska-Ketende, K., & Cousens, S. N. (2006) · International Journal of Epidemiology · doi:10.1093/ije/dyl043 · Cited by 515 · see citing works
NICHD Neonatal Research Network
Wright, L. L. (2002) · Medical Entomology and Zoology · Cited by 384 · see citing works
Origins and unconventional behavior of neutrophils in developing zebrafish
Guyader, D. L., Redd, M. J., Colucci‐Guyon, E., Murayama, E., Kissa, K., Briolat, V., Mordelet, E., Zapata, A. G., Shinomiya, H., & Herbomel, P. (2007) · Blood · doi:10.1182/blood-2007-06-095398 · Cited by 380 · see citing works
Miller, L. J., Schwarting, R., & Springer, T. A. (1986) · The Journal of Immunology · doi:10.4049/jimmunol.137.9.2891 · Cited by 293 · see citing works
The neutrophil: function and regulation in innate and humoral immunity.
Burg, N. D., & Pillinger, M. (2001) · Clinical Immunology · doi:10.1006/clim.2001.5007 · Cited by 286 · see citing works
Makhseed, M., Raghupathy, R., Azizieh, F. Y., Omu, A. E., Al-Shamali, E., & Ashkanani, L. (2001) · Human Reproduction · doi:10.1093/humrep/16.10.2219 · Cited by 281 · see citing works
The functional significance behind expressing two IL–8 receptor types on PMN
Stillie, R., Farooq, S. M., Gordon, J., & Stadnyk, A. W. (2009) · Journal of Leukocyte Biology · doi:10.1189/jlb.0208125 · Cited by 271 · see citing works
E-selectin supports neutrophil rolling in vitro under conditions of flow.
Abbassi, O., Kishimoto, T., McIntire, L. V., Anderson, D. C., & Smith, C. W. (1993) · Journal of Clinical Investigation · doi:10.1172/jci116889 · Cited by 262 · see citing works
P-selectin Glycoprotein Ligand-1 Mediates L-Selectin–dependent Leukocyte Rolling in Venules
Sperandio, M., Smith, M. L., Forlow, S. B., Olson, T. S., Xia, L., McEver, R. P., & Ley, K. F. (2003) · The Journal of Experimental Medicine · doi:10.1084/jem.20021854 · Cited by 238 · see citing works
Self-citationXia, L., Sperandio, M., Yago, T., McDaniel, J. M., Cummings, R. D., Pearson-White, S. H., Ley, K. F., & McEver, R. P. (2002) · Journal of Clinical Investigation · doi:10.1172/jci14151 · Cited by 230 · see citing works
Self-citationBallard, P. L., Granberg, P. O., & Ballard, R. A. (1975) · Journal of Clinical Investigation · doi:10.1172/jci108236 · Cited by 230 · see citing works
Neutrophil Adhesion and Activation under Flow
Zarbock, A., & Ley, K. F. (2008) · Microcirculation · doi:10.1080/10739680802350104 · Cited by 218 · see citing works
Xia, L., Sperandio, M., Yago, T., McDaniel, J. M., Cummings, R. D., Pearson-White, S. H., Ley, K. F., & McEver, R. P. (2002) · Journal of Clinical Investigation · doi:10.1172/jci0214151 · Cited by 199 · see citing works
Self-citationWynn, J. L., Scumpia, P. O., Winfield, R. D., Delano, M. J., Kelly‐Scumpia, K. M., Barker, T. T., Ungaro, R. F., Levy, O., & Moldawer, L. L. (2008) · Blood · doi:10.1182/blood-2008-01-130500 · Cited by 173 · see citing works
Hyper innate responses in neonates lead to increased morbidity and mortality after infection
Zhao, J., Kim, K. D., Yang, X., Auh, S. L., Fu, Y., & Tang, H. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0800152105 · Cited by 164 · see citing works
Infections in Patients With Aplastic Anemia
Valdez, J. M., Scheinberg, P., Young, N. S., & Walsh, T. J. (2009) · Seminars in Hematology · doi:10.1053/j.seminhematol.2009.03.008 · Cited by 108 · see citing works
Aziz, K. E., & Wakefield, D. (1996) · Cellular Immunology · doi:10.1006/cimm.1996.0010 · Cited by 108 · see citing works
Anderson, D. C., Abbassi, O., Kishimoto, T. K., et al. (1991) · The Journal of Immunology · doi:10.4049/jimmunol.146.10.3372 · Cited by 106 · see citing works
Decreased Adherence, Chemotaxis and Phagocytic Activities of Neutrophils from Preterm Neonates
BEKTAS, S., Goetze, B., & Speer, C. P. (1990) · Acta Paediatrica · doi:10.1111/j.1651-2227.1990.tb11379.x · Cited by 106 · see citing works
Disorders of Neutrophil Function
Dinauer, M. C. (2007) · Methods in molecular biology · doi:10.1007/978-1-59745-467-4_30 · Cited by 105 · see citing works
Divergent Inducible Expression of P-Selectin and E-Selectin in Mice and Primates
Yao, L., Setiadi, H., Xia, L., Laszik, Z. G., Taylor, F. B., & McEver, R. P. (1999) · Blood · doi:10.1182/blood.v94.11.3820 · Cited by 105 · see citing works
Anderson, D., Freeman, K., Heerdt, B. G., Hughes, B. J., Jack, R., & Smith, C. W. (1987) · Blood · doi:10.1182/blood.v70.3.740.740 · Cited by 99 · see citing works
McEvoy, L., Zakem-Cloud, H., & Tosi, M. (1996) · Blood · doi:10.1182/blood.v87.9.3929.bloodjournal8793929 · Cited by 75 · see citing works
Fox, S. E., Lu, W., Maheshwari, A., Christensen, R. D., & Calhoun, D. A. (2004) · Cytokine · doi:10.1016/j.cyto.2004.10.007 · Cited by 74 · see citing works
Neutrophil chemotaxis and adhesion in preterm babies.
Carr, R. A., Pumford, D., & Davies, J. M. (1992) · Archives of Disease in Childhood · doi:10.1136/adc.67.7_spec_no.813 · Cited by 64 · see citing works
P-Selectin Expression by Endothelial Cells Is Decreased in Neonatal Rats and Human Premature Infants
Lorant, D. E., Li, W., Tabatabaei, N., et al. (1999) · Blood · doi:10.1182/blood.v94.2.600 · Cited by 63 · see citing works
Distributions of Wall Shear Stress in Venular Convergences of Mouse Cremaster Muscle
Kim, M. B., & Sarelius, I. H. (2003) · Microcirculation · doi:10.1038/sj.mn.7800182 · Cited by 56 · see citing works
Innate immune cell recruitment in the fetus and neonate
Nußbaum, C., & Sperandio, M. (2011) · Journal of Reproductive Immunology · doi:10.1016/j.jri.2011.01.022 · Cited by 50 · see citing works
Self-citationAl‐Hertani, W., Yan, S. R., Byers, D. M., & Bortolussi, R. A. (2007) · Clinical and investigative medicine · doi:10.25011/cim.v30i2.979 · Cited by 49 · see citing works
Use of Prenatal Glucocorticoid Therapy to Prevent Respiratory Distress Syndrome
Ballard, R. A. (1976) · American journal of diseases of children · doi:10.1001/archpedi.1976.02120100072011 · Cited by 48 · see citing works
Impaired CD14-dependent and independent response of polymorphonuclear leukocytes in preterm infants
Henneke, P., Osmers, I., Bauer, K., Lamping, N., VERSMOLD, H. T., & Schumann, R. R. (2003) · Journal of Perinatal Medicine · doi:10.1515/jpm.2003.024 · Cited by 45 · see citing works
Polymorphonuclear Leukocyte Function in the Preterm Neonate: Effect of Chronologic Age
Usmani, S. S., Schlessel, J. S., Sia, C. G., et al. (1991) · PEDIATRICS · doi:10.1542/peds.87.5.675 · Cited by 44 · see citing works
Smith, M. L., Sperandio, M., Galkina, E., & Ley, K. F. (2004) · Journal of Leukocyte Biology · doi:10.1189/jlb.1003483 · Cited by 43 · see citing works
Self-citationLongitudinal study of neutrophil adherence and motility
Eisenfeld, L., Krause, P. J., HERSON, V. C., et al. (1990) · The Journal of Pediatrics · doi:10.1016/s0022-3476(05)80139-8 · Cited by 42 · see citing works
Mariscalco, M. M., Tcharmtchi, M. H., & Smith, C. W. (1998) · Blood · doi:10.1182/blood.v91.12.4776 · Cited by 42 · see citing works
Naik-Mathuria, B. J., Gay, A. N., Zhu, X., Yu, L., Cass, D. L., & Olutoye, O. O. (2007) · Journal of Pediatric Surgery · doi:10.1016/j.jpedsurg.2006.09.058 · Cited by 32 · see citing works
Distributions of Wall Shear Stress in Venular Convergences of Mouse Cremaster Muscle
Kim, M. S., & Sarelius, I. H. (2003) · Microcirculation · doi:10.1080/713773612 · Cited by 31 · see citing works
The Effect of Betamethasone on Neonatal Neutrophil Chemotaxis
Fuenfer, M. M., HERSON, V. C., Raye, J. R., et al. (1987) · Pediatric Research · doi:10.1203/00006450-198708000-00009 · Cited by 20 · see citing works
Tcharmtchi, M. H., Smith, C. W., & Mariscalco, M. M. (2000) · Journal of Leukocyte Biology · doi:10.1002/jlb.67.1.73 · Cited by 20 · see citing works
USE OF PRENATAL GLUCOCORTICOID THERAPY TO PREVENT RESPIRATORY DISTRESS SYNDROME
Ballard, R. A., & Ballard, P. L. (1977) · Obstetrical & Gynecological Survey · doi:10.1097/00006254-197704000-00012 · Cited by 18 · see citing works
Genzel‐Boroviczény, O., MACWILLIAMS, S., von Poblotzki, M., et al. (2006) · Acta Obstetricia Et Gynecologica Scandinavica · doi:10.1080/00016340500290947 · Cited by 18 · see citing works
Self-citationStorm, S. W., Mariscalco, M. M., & Tosi, M. F. (2008) · Journal of Leukocyte Biology · doi:10.1189/jlb.0308170 · Cited by 15 · see citing works
Jaarsma, A. S., Braaksma, M. A., Geven, W. B., et al. (2003) · Neonatology · doi:10.1159/000074963 · Cited by 4 · see citing works
Rouwet, E. V., Beuk, R. J., Heineman, E., et al. (2000) · Journal of Pediatric Surgery · doi:10.1016/s0022-3468(00)80012-3 · Cited by 3 · see citing works
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Evolution of the immune system in humans from infancy to old age
Simon, A. K., Hollander, G. A., & McMichael, A. (2015) · Proceedings of the Royal Society B: Biological Sciences · doi:10.1098/rspb.2014.3085 · Cited by 1,796 · see citing works
Ortmann, W., & Kolaczkowska, E. (2018) · Cell and Tissue Research · doi:10.1007/s00441-017-2751-4 · Cited by 80 · see citing works
- Authors
- Nussbaum, C., Gloning, A., Pruenster, M., Frommhold, D., Bierschenk, S., Genzel-Boroviczény, O., von Andrian, U. H., Quackenbush, E., & Sperandio, M.
- Affiliations
- Institut für Chirurgische Forschung (DE)
- Heidelberg University (DE)
- Division of Neonatology, Perinatal Center at the Department of Gynecology and Obstetrics, University Childrenˈs Hospital, Ludwig-Maximilians-Universität , Munich, Germany
- Department of Microbiology and Immunobiology, Harvard Medical School , Boston, Massachusetts, USA
- Agennix (United States) (US)
- Corresponding author
- Sperandio, Markus
- Venue
- Journal of Leukocyte Biology
- Publisher
- Oxford University Press (OUP)
- Published
- 2013-02-01
- Volume
- 93
- Issue
- 2
- Pages
- 175-184
- ISSN
- 0741-5400 (ISSN-L)
- 1938-3673
- PMC
- PMC4050519
- OpenAlex
- W2102316212
- Cited by
- 100
- References
- 53
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 12 · 2023: 5 · 2022: 9 · 2021: 10 · 2020: 15 · 2019: 10 · 2018: 6 · 2017: 5 · 2016: 6 · 2015: 4 · 2014: 6 · 2013: 3
- FWCI
- 3.07
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Leukocyte Biology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Friedrich-Baur-Stiftung
- B. Braun-Stiftung
- DFG Collaborative Research Center (914, SFB 914)
- Topics
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Life Sciences › Immunology and Microbiology › Immunology › Inflammation biomarkers and pathways
- Keywords
- neutrophil recruitment, neutrophil adhesion, endothelial cell adhesion, neutrophil rolling, fetal development, gestational age, preterm infants, neonatal infection, PSGL-1, Mac-1, E-selectin, ICAM-1, human umbilical vein endothelial cells, innate immunity, ontogeny
- MeSH terms
- Cell Adhesion, Female, Fetus, Flow Cytometry, Fluorescent Antibody Technique, Gestational Age, Humans, Infant, Newborn, Infant, Premature, Male, Neutrophils, Intercellular Adhesion Molecule-1, P-Selectin, E-Selectin, Neutrophil Infiltration, Leukocyte Rolling, Endothelial Cells, Human Umbilical Vein Endothelial Cells, Infant, Extremely Premature
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