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CD18-dependent and L-selectin-dependent neutrophil emigration is diminished
in neonatal rabbits
JD Fortenberry, JR Marolda, DC Anderson, CW Smith and MM Mariscalco
Department of Pediatrics, Baylor College of Medicine, Houston, TX.
Human neonatal neutrophils manifest decreases in mobility, adherence, and
emigration compared with adult neutrophils that may contribute to the
increased susceptibility of neonates to infection. In a developmental
rabbit model, we show a reduced ability of neutrophils from 1-day-old
rabbit pups to emigrate to inflamed peritoneium (3.7 +/- 0.35 x 10(6)
neutrophils/mL peritoneal exudate) compared with 14-day- old (8.5 +/- 0.7 x
10(6)/mL) and adult rabbits (9.4 +/- 1.4 x 10(6) mL, P < .05) despite
significantly increased blood neutrophil counts. Because the reductions in
functional Mac-1 (CD11b/CD18) as well as the amount of surface L-selectin
are hypothesized to be primarily responsible for the differences in human
neonatal neutrophil mobility, we examined CD11b/CD18 and L-selectin in our
model. Using flow cytometric analysis we found that similar to human
neonates, neutrophils from 1-day-old rabbit pups had 57% of adult rabbit
levels of L-selectin and, in contrast with adults, failed to show
significant decreases in L-selectin after chemotactic stimulation. In
addition, neutrophils from 1-day-old pups compared with adults showed a
significantly diminished capacity to upregulate CD11b/CD18 after
chemotactic stimulation in vitro, or after emigration to the inflamed
peritoneum. Systemic administration of anti-L-selectin monoclonal antibody
(MoAb) resulted in significant reduction in peritoneal neutrophils in adult
(47%, P < .05) and 14-day-old rabbits (47%, P < .05), but was without
effect in 1-day-old rabbits. Administration of anti-CD18 MoAb resulted in
significant reduction in peritoneal neutrophil accumulation in all age
groups though less in 1 day and 14 day (58% and 65%, respectively) than in
adults (91%, P < .05). Only in the 14-day-old rabbits was there an
additive effect of anti-L-selectin and anti-CD18 MoAbs compared with
anti-CD18 alone (84% v 65%, P < .05). The findings in this in vivo
rabbit model support the hypothesis that the previously described in vitro
defects in human neonatal L-selectin and CD11b/CD18 may be major
contributors to human neonatal inflammatory deficits.
Volume 84,
Issue 3,
pp. 889-897,
08/01/1994
Copyright © 1994 by The American Society of Hematology
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