Chemotactic competence of neutrophils from neonatal calves

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Abstract
Neonates demonstrate an increased susceptibility to infection. Defects in locomotory functions of newborn neutrophils may play a crucial role in this context. We therefore compared the migratory response of newborn (N-PMN) and adult (APMN) bovine neutrophils in a microwell filter assay. Stimulation with four different endotoxins (E. coli O128 B∶:4 and O55 B∶5;S. abortus equi; S. typhimurium), with zymosan-activated plasma (ZAP) and with C5a induced dose-dependent migration of A-PMNs and N-PMNs. Migration of unstimulated cells and of cells stimulated with diluted ZAP or C5a was higher (P < 0.05) in N-PMNs. Migration of A- and N-PMNs towards C5a was inhibited (P < 0.001) by preincubation with either a steroidal (122μM flumethasone) or nonsteroidal (3.3μM phenylbutazone) antiinflammatory drug. Migratory responses of N-PMNs were inhibited less by SAIDs than were responses of A-PMNs (P < 0.05); indeed dexamethasone slightly enhanced N-PMN responses towards C5a, and 510μM flunixin meglumine enhanced C5a-induced migration in both age groups. Endotoxins fromE. coli O55:B4,S. abortus equi, and S. typhimurium induced a higher rate of migration (P < 0.05) in N-PMNs. In contrast to the above findings, measurement of the maximal distance of migration by the leading-front method did not reveal age-related differences. Migration speed of PMNs was lower after stimulation with C5a than with ZAP, but could be restored partly by adding human vitamin D-binding protein (Gc-globulin). The demonstrated hyperirritability of bovine N-PMNs represents a major functional difference to neonatal neutrophils from other species, including man. It may additionally be related to altered PMN functions and neonatal disease susceptibility.