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Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom
Macrophage (M
) expression of the leukocyte integrins has been
implicated in their adhesion and migration in the adult. Little is
known, however, of the expression or function of these molecules during
development. This study defines the spatial and temporal sequences of
expression of the type 3 complement receptor (CR3) in the developing
mouse; establishes the functional efficacy of this molecule in
spreading, adhesion, and phagocytosis; and investigates its role in
inflammatory and constitutive migration. Expression of CR3 on monocytes
occurred early compared to M
-restricted glycoprotein F4/80, but
expression on stellate tissue M
appeared later than F4/80 and was
transient. Expression of CR3 on resident tissue M
is more widespread
during development, being retained on only very specific M
populations in the adult. Neutrophil polymorphs expressed CR3 from day
17 of gestation onward. The anti-CR3 mAb 5C6 was used to
investigate the role of CR3 in adhesion, spreading, and phagocytosis by
neonatal M
. Neonatal macrophages were found to adhere, spread, and
phagocytose by CR3-dependent mechanisms, and a CR3-independent system
was implicated in the spreading of neonatal M
. The role of CR3 in
migration during development was then investigated. 5C6 had potent
effects on the early stages of the migration of myelomonocytic cells to
an inflammatory stimulus in vivo. Despite efficient transplacental
transfer of the Ab from pregnant mother to fetus, the process by which
monocytes generate populations of resident tissue M
was undisrupted,
indicating the existence of CR3-independent mechanisms of monocyte
migration during development.
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