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American Journal of Pathology, Vol 128, 307-314, Copyright © 1987 by American Society for Investigative Pathology

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Correction of a developmental defect in neutrophil activation and movement

HR Hill, NH Augustine, JA Newton, AO Shigeoka, E Morris and F Sacchi

In order to more fully understand the mechanisms involved in the developmental defect in polymorphonuclear leukocyte (PMN) movement in human neonates, the authors have examined several events in the activation response sequence. Chemotactic factor receptor numbers have been found to be normal on the PMNs of neonates, but chemotactic factor- induced changes in membrane potential and cyclic adenosine monophosphate concentrations were markedly decreased to absent in the neonatal cells. Because the neonatal PMN lacks the ability to deform normally, we examined the effects of a methylxanthine derivative, pentoxifylline, on the responses of neonatal cells. This agent has been reported to increase cell deformability and improve cell movement. Pentoxifylline had an effect in improving chemotactic function in the PMNs of neonates, while correcting the abnormality in membrane potential. In addition, this agent was found to enhance the movement of cell surface concanavalin A receptors after colchicine treatment. These results suggest that this developmental defect in cell activation and movement may be an abnormality that can be corrected pharmacologically.