Brain vessels near muscle autografts are sites for entry of isogeneic macrophages into brain.
An autograft of skeletal muscle on rat dorsal medulla is a permanent opening in the blood-brain barrier to solutes. Is the graft also a site for the entry of exogenous, isogeneic leukocytes? Five weeks after inserting the graft, peritoneal macrophages (M phi) from inbred Fischer rats were activated by phorbol myristate acetate, labeled with a fluorescent dye, and infused as a bolus of about 2 x 10(6) cells into the axillary artery of Fischer hosts. The cells circulated for 2 h. The brains were then fixed, frozen, and sectioned. Only when M phi had been activated and a muscle autograft inserted did appreciable numbers of M phi enter the medulla. Nonactivated M phi invaded the grafts but very few entered the brain at 2 h. In rats with gel foam grafts, only a few activated M phi invaded gel and brain. Before entering tissues, M phi must adhere to the lumenal face of vessels. Cell adhesion molecules, e.g., I-CAM-1 and its ligand adhesion molecule, leukocyte function antigen (LFA-1), are known to mediate adhesion. I-CAM-1, detected immunohistochemically, increased in graft vessels and in nearby brain vessels. The rise may have been mediated by cytokines, interleukin-6, and tumor necrosis factor-beta, found in the grafts. LFA-1, however, assayed by fluorescence-activated cell sorting, was on both activated and nonactivated, exogenous M phi. Thus, M phi-endothelial attachment may have involved other adhesion molecules, e.g., selectins. The autograft also induced major histocompatibility complex class I on microglia and classes I and II on brain vessels near the graft. These vessels, by expressing adhesion molecules, are entry routes into brain for activated, isogeneic leukocytes that can then migrate for a limited distance of 1-2 mm in an otherwise intact brain.
Ishihara
S
S
Laboratory of Neurobiology, NINDS, National Institutes of Health, Bethesda, Maryland 20892.
Sawada
M
M
Chang
L
L
Kim
J M
JM
Brightman
M
M
D000818:Animals; D000911:Antibodies, Monoclonal; D002196:Capillaries / Q000502:physiology; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000032:analysis / Q000096:biosynthesis; D002465:Cell Movement; D002531:Cerebellum / Q000098:blood supply; D002552:Cerebral Ventricles / Q000502:physiology*; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma / Q000032:analysis / Q000378:metabolism; D016169:Lymphocyte Function-Associated Antigen-1 / Q000032:analysis / Q000096:biosynthesis; D008233:Lymphotoxin-alpha / Q000032:analysis / Q000378:metabolism; D008262:Macrophage Activation; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000502:physiology* / Q000637:transplantation; D008297:Male; D008526:Medulla Oblongata / Q000098:blood supply*; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D009132:Muscles / Q000637:transplantation*; D009389:Neovascularization, Pathologic; D051381:Rats; D011916:Rats, Inbred F344; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014182:Transplantation, Autologous / Q000502:physiology*; D014185:Transplantation, Isogeneic
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D016169:Lymphocyte Function-Associated Antigen-1; D008233:Lymphotoxin-alpha; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma; D013755:Tetradecanoylphorbol Acetate