Expression and function of the type 3 complement receptor in tissues of the developing mouse.
Macrophage (Mphi) 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 Mphi-restricted glycoprotein F4/80, but expression on stellate tissue Mphi appeared later than F4/80 and was transient. Expression of CR3 on resident tissue Mphi is more widespread during development, being retained on only very specific Mphi 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 Mphi. 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 Mphi. 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 Mphi was undisrupted, indicating the existence of CR3-independent mechanisms of monocyte migration during development.
Hughes
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Sir William Dunn School of Pathology, University of Oxford, United Kingdom.
Gordon
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D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D005314:Embryonic and Fetal Development / Q000276:immunology*; D005260:Female; D005333:Fetus / Q000276:immunology*; D007150:Immunohistochemistry; D016177:Macrophage-1 Antigen / Q000096:biosynthesis* / Q000276:immunology*; D051379:Mice; D009928:Organ Specificity; D011247:Pregnancy
D000911:Antibodies, Monoclonal; D016177:Macrophage-1 Antigen