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Subcellular distribution and mobilization of MAC-1 (CD11b/CD18) in neonatal
neutrophils
DH Jones, FC Schmalstieg, K Dempsey, SS Krater, DD Nannen, CW Smith and DC Anderson
Department of Pediatrics, Microbiology and Immunology, and Cell Biology,
Baylor College of Medicine, Speros P. Martel Leukocyte Biology Laboratory,
Texas Children's Hospital, Houston.
The CD11b/CD18 (Mac-1) heterodimeric surface glycoprotein contributes to a
broad range of adherence-dependent neutrophil inflammatory functions.
Previous investigations have indicated that diminished expression or
regulation of Mac-1 may underlie abnormalities of stimulated adhesion and
chemotaxis of neonatal neutrophils in vitro and inflammatory deficits in
human neonates. To define the pathogenic mechanisms contributing to these
findings, we compared the distribution and translocation of Mac-1 in
subcellular fractions of neonatal and adult neutrophils before and after
chemotactic stimulation. The total cell content of Mac-1 and the
proportions of Mac-1 in beta fractions (vitamin B12 binding protein-rich
granules), pre-gamma fractions (gelatinase-rich granules), or gamma
fractions (plasma membrane) of neonatal neutrophils were comparable with
those of adult neutrophils. However, after stimulation with
N-formyl-methionyl-leucyl-phenylalanine (FMLP; 10 nmol/L, 37 degrees C, 15
minutes), neonatal neutrophils demonstrated (1) diminished translocation of
Mac-1 from pre-gamma fractions (P less than .05), and (2) diminished
surface expression of Mac-1 (P less than .05), as compared with healthy
adult neutrophils. As shown in enzymatic and immunochemical assays,
neonatal cells contained significantly (P less than .01) diminished levels
of neutrophil gelatinase. In response to FMLP (0.1 to 10 nmol/L, 37 degrees
C, 15 minutes), neonatal suspensions also released significantly (P less
than .001) less gelatinase, as compared with adult neutrophil suspensions.
These observations demonstrate that diminished mobilization of Mac-1 from
gelatinase-rich granular pools in neonatal neutrophils is associated with
abnormal surface expression of this glycoprotein after chemotactic
stimulation. This abnormality may contribute, in part, to abnormal
migratory properties of neonatal neutrophils in response to inflammatory
stimuli.
Volume 75,
Issue 2,
pp. 488-498,
01/15/1990
Copyright © 1990 by The American Society of Hematology
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