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Ontogeny of inflammatory cell responsiveness

Superoxide anion generation by phorbol ester-stimulated fetal, neonatal, and adult bovine neutrophils

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Abstract

Newborn calves, like human infants, are uniquely susceptible to bacterial infections. Part of this increased susceptibility may be related to defects in newborn polymorphonuclear leukocyte (PMN) defensive functions. It remains unclear whether reported deficits in newborn PMN function represent maturational disorders or are manifestations of some form of perinatal suppression phenomenon. We therefore compared the ability of bovine newborn PMNs (less than 24 h old), newborn PMNs (7–10 days of age), fetal PMNs (210–220 days gestational age), and adult PMNs to generate superoxide anion (O −2 ) as an indicator of respiratory burst activity. Citrated biood was collected, and PMNs were isolated to greater than 95% purity and 98% viability. O −2 generation was measured as the superoxide dismutase-inhibitable (10 μg/ml) reduction of ferricytochrome c (2 mg/ml) after activation of PMNs with phorbol myristate acetate (PMA, 2 μg/ml) to directly stimulate protein kinase C. The reaction kinetics were measured (37°C, 550 nm) using a spectrophotometer and chart recorder for continuous monitoring. O −2 generation was measured for 5 min after the initial lag period and the total nanomoles of O −2 generated calculated using the extinction coefficient for ferricytochromec. Newborn PMNs (N=10) generated significantly less O −2 (5.7 ±0.8 nmol O −2 /106 cells/5 min,P < 0.01) than did adult PMNs (N=14) (9.6 ±2.1 nmol O −2 /1010 cells/5 min) or fetal PMNs (N=4) (10.7 ±0.7 nmol O −2 /106 cells/5 min). PMNs from 7-to 10-day-old calves (N=9) generated almost identical amounts of O −2 as newborn PMNs (5.7 ±1.6 nmol O −2 /106 ceils/5 min). There was no difference in measured lag time period between new-born and adult PMNs, but fetal PMNs had significantly reduced (P < 0.01) mean lag time. The data indicated that bovine newborn PMNs have a decreased ability to generate O −2 in response to PMA stimulation, which persists for at least 7–10 days, and that this functional decrement may be a manifestation of some form of perinatal PMN suppression phenomenon rather than a developmental abnormality since fetal PMNs produced O −2 as well as adult PMNs.

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Authors and Affiliations

  1. Inflammation Research Laboratory, College of Veterinary Medicine, Cornell University, 14853, Ithaca, New York

    Charles B. Clifford, David O. Slauson, Nancy R. Neilsen & M. Mitsu Suyemoto

  2. Laboratory of Reproductive Pathology,Department of Pathology, College of Veterinary Medicine, Cornell University, 14853, Ithaca, New York

    Donald H. Schlafer

  3. Institut für Tierpathologie, Universität Bern, Länggastrasse 122, Bern, Switzerland

    Roland D. Zwahlen

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Clifford, C.B., Slauson, D.O., Neilsen, N.R. et al. Ontogeny of inflammatory cell responsiveness. Inflammation 13, 221–231 (1989). https://doi.org/10.1007/BF00924792

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