title: CD18-dependent and L-selectin-dependent neutrophil emigration is diminished in neonatal rabbits.
abstract: 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.
authors.affiliation: Department of Pediatrics, Baylor College of Medicine, Houston, TX.
authors.forename: J D
authors.initials: JD
authors.lastname: Fortenberry
authors.forename: J R
authors.initials: JR
authors.lastname: Marolda
authors.forename: D C
authors.initials: DC
authors.lastname: Anderson
authors.forename: C W
authors.initials: CW
authors.lastname: Smith
authors.forename: M M
authors.initials: MM
authors.lastname: Mariscalco
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD / Q000502:physiology*; D018821:CD18 Antigens; D015815:Cell Adhesion Molecules / Q000502:physiology*; D002465:Cell Movement; D002634:Chemotaxis, Leukocyte; D005260:Female; D019041:L-Selectin; D016177:Macrophage-1 Antigen / Q000378:metabolism; D009504:Neutrophils / Q000166:cytology* / Q000378:metabolism; D010538:Peritonitis / Q000503:physiopathology; D011817:Rabbits
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018821:CD18 Antigens; D015815:Cell Adhesion Molecules; D016177:Macrophage-1 Antigen; D019041:L-Selectin