DIMINISHED PRIMING OF NEONATAL POLYMORPHONUCLEAR LEUKOCYTES BY LIPOPOLYSACCHARIDE IS ASSOCIATED WITH REDUCED CD14 EXPRESSION

Previous research in our laboratory has shown that polymorphonuclear l eukocytes (PMN) from neonates are not primed effectively in vitro with lipopolysaccharide (LPS) (from Escherichia call 0111:B4) compared wit h priming of adult PMN. This finding led us to speculate that differen ces between neonatal and adult LPS receptors may account for the lower response by neonatal PMN to LPS. In these experiments, we investigate d if CD14 or other LPS receptors contribute to the priming activity of PMN by LPS, We found that unprimed neonatal and adult PMN expressed s imilar numbers of CD14 (11.6 +/- 9.2 versus 18.6 +/- 2.7 fluorescence units [FIU]; P > 0.05) and LPS-binding sites (2.9 +/- 1.4 versus 4.94 +/- 0.79 FIU; P > 0.05). Monoclonal antibody against CD14 (MY4) did no t significantly change the binding of LPS to adult unprimed PMN, sugge sting that LPS receptors other than CD14 receptors are predominant on PMN. However, when PMN were pretreated with LPS (10 ng/ml) for 45 min at 37 degrees C, expression of CD14 on adult PMN increased to 33.8 +/- 4.9 FIU (P < 0.05 versus unprimed adult PMN) while that on neonatal P MN showed little change, increasing to 17.2 +/- 10.3 FIU (P > 0.05 ver sus unprimed neonatal PRMN; P < 0.05 versus primed adult PMN). Further more, MY4 specifically blocked oxidative-radical production from PMN p rimed with LPS (10 ng/ml) compared with that from control PMN (P < 0.0 1). These studies suggest that LPS primes PMN by activating CD14 expre ssion. We conclude that lower expression of CD14 or failure to up-regu late CD14 after LPS pretreatment contributes to the inability of neona tal PMN to be primed by LPS.