Contribution of lfa-1 and mac-1 to cd18- dependent neutrophil
emigration in a neonatal rabbit model.
Graf, J. M., C. W. Smith, and M. M. Mariscalco.
Departments of Pediatrics, Sections of Leukocyte Biology and
Critical Care, Baylor College of Medicine, Houston, Texas 77030
-2399
APStracts 3:0039A, 1996.
Human neonatal polymorphonuclear leukocytes (PMNs) exhibit decreased
mobility, adherence and transendothelial migration in vitro compared
to adult PMNs. These deficits, in part, are due to functional and
quantitative defects in neonatal Mac-1 (CD11b/CD18), while LFA-1
(CD11a/CD18) function is similar to that found in adults (2,38). We
tested the hypothesis that the primary mechanism for the neonatal PMN
CD18-dependent emigration in vivo is due to LFA-1. Neutrophils from
one day old rabbit pups had 32% and 60% respectively of adult rabbit
levels of CD11a and CD11b respectively. Rabbit pups or adult rabbits
received the monoclonal antibodies (MoAbs) R7.1(anti-CD11a),
R15.7(anti-CD18), or the vehicle phosphate-buffered saline (PBS)
prior to the instillation of intraperitoneal thioglycollate. Six
hours later peritoneal exudate was collected. The administration of
MoAbs R7.1 and R15.7 in adult animals resulted in 60% and 83%
inhibition of leukocyte emigration compared to PBS-treated animals
(p<0.01). In neonatal animals R7.1 and R15.7 inhibited leukocyte
peritoneal accumulation to the same extent (50% and 60% respectively)
compared to PBS-treated animals (p<0.01). Adult animals were
also treated with the anti-CD11b MoAb, 198. MoAb decreased emigration
by 25% though this was not significant compared to PBS-treated
animals (356 +/- 47, p=0.6). We conclude that though neonatal animals
have significantly less neutrophil CD11a, the diminished levels did
not contribute to a reduced ability to emigrate to the peritoneum,
and like adult animals, primarily utilize LFA-1 for accumulation in
this model. The contribution of Mac-1 to neonatal leukocyte
emigration remains uncertain.
Received 5 June 1995; accepted in final form 3 January 1996.
APS Manuscript Number A595-5.
Article publication pending Journal of Applied Physiology.
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 25 January 96