CD8+ phagocytes in focal ischemia of the rat brain : predominant origin from hematogenous macrophages and targeting to areas of pannecrosis

• Published in: Acta neuropathologica Vol. 101; no. 5; pp. 440 - 448
• Main Authors: SCHROETER, M, JANDER, S, HUITINGA, I, STOLL, G
• Format: Journal Article
• Language: English
• Published: Berlin Springer 01.05.2001; Springer Nature B.V
• Subjects: Animals; Antigens; Antigens, CD; Antigens, Neoplasm; Antigens, Surface; Avian Proteins; Basigin; Biological and medical sciences; Blood Proteins; Brain Ischemia - immunology; Brain Ischemia - pathology; Brain Ischemia - physiopathology; CD4 antigen; CD4 Antigens - immunology; CD4 Antigens - metabolism; CD8 antigen; CD8 Antigens - immunology; CD8 Antigens - metabolism; Cell death; Cerebral blood flow; Clodronic Acid - pharmacology; Ectodysplasins; Glial Fibrillary Acidic Protein - metabolism; Immunohistochemistry; Immunoreactivity; Infarction, Middle Cerebral Artery - immunology; Infarction, Middle Cerebral Artery - pathology; Infarction, Middle Cerebral Artery - physiopathology; Ischemia; Lesions; Liposomes; Lymphocytes - cytology; Lymphocytes - drug effects; Lymphocytes - immunology; Macrophage Activation - immunology; Macrophages; Macrophages - drug effects; Macrophages - immunology; Medical sciences; Membrane Glycoproteins - metabolism; Membrane Proteins - metabolism; Microglia; Microglia - immunology; Microglia - metabolism; Monoclonal antibodies; Necrosis; Neurology; Phagocytes; Phagocytes - cytology; Phagocytes - drug effects; Phagocytes - immunology; Phagocytosis - immunology; Rats; Rats, Wistar; Vascular diseases and vascular malformations of the nervous system; Immunohistochemistry; Nervous system diseases; Pathophysiology; Rat; Rodentia; Cardiovascular disease; Exploration; Transitory; Cerebral disorder; Microglia; Vascular disease; Pathology; Vertebrata; Mammalia; Ischemia; Animal; Central nervous system disease; Cerebrovascular disease; Brain (vertebrata); Macrophage; Cell origin; Phagocyte
• ISSN: 0001-6322; 1432-0533
• DOI: 10.1007/s004010000304

We have recently described a novel population of CD8+ phagocytes that are strongly recruited to focal ischemic lesions of the rat brain but absent from axotomized central fiber tracts. To assess the relative contribution of infiltrating macrophages and resident microglia to the CD8+ phagocyte response, we selectively depleted peripheral macrophages by systemic administration of dichloromethylene diphosphonate-filled liposomes prior to the induction of permanent ischemia by photothrombosis of cortical microvessels. Macrophage depletion led to a dramatic reduction but not complete abolishment of CD8+ cells in the ensuing infarcts. Systemic administration of monoclonal antibody Ox-8 eliminated CD8+ cells from peripheral lymphoid organs but had no effect on CD8+ phagocytes in the ischemic brain lesions. To further characterize the lesion conditions inducing the recruitment of CD8+ phagocytes, we induced mild focal ischemia by transient occlusion of the middle cerebral artery that leads to a core infarction with ischemic pannecrosis surrounded by areas with selective neuronal cell death. Recruitment of CD8+ phagocytes was restricted to areas of ischemic pannecrosis. In areas undergoing selective neuronal loss microglia up-regulated complement receptor-3, exhibited ED1 immunoreactivity (indicating phagocytic activity), and to some extent expressed CD4, but not CD8 antigens. In conclusion our present study shows that CD8+ phagocytes in focal brain ischemia are predominantly derived from hematogenous macrophages and selectively target to areas of ischemic pannecrosis.