I. Huitinga

Liposome-mediated monocyte depletion during wallerian degeneration defines the role of hematogenous phagocytes in myelin removal.

Newly recruited hematogenous mononuclear cells of the monocyte/macrophage system are suggested to be important effector cells in myelin removal during Wallerian degeneration. Their role has extensively been studied in various in vitro and in vivo models. However, there has been much controversy concerning the role of hematogenous vs. resident cells of the peripheral nervous system in Wallerian degeneration. The present study used a recently established technique to deplete the hematogenous monocyte population by application of dichloromethylene diphosphonate‐containing liposomes. Intravenously injected liposomes containing dichloromethylene diphosphonate (Cl2MDP) are ingested by macrophages and monocytes and cause temporary and selective depletion of these cells. The number of LFA‐1‐and Mac‐l‐ positive macrophages within the nerves was significantly reduced when liposomes were injected shortly after nerve transsection. In these nerves, myelin degradation was significantly less, indicating an essential role of newly recruited phagocytes in this process. Macrophage invasion of degenerating nerves occurred within the first 2 days after transsection. Resident cells of the peripheral nerve participate in myelin removal since macrophage depletion did not completely abolish myelin degradation. These results confirm the important role of hematogenous phagocytes in myelin removal during Wallerian degeneration.

Therapeutic effect of the D2-dopamine agonist bromocriptine on acute and relapsing experimental allergic encephalomyelitis.

We examined the effect of bromocriptine (BCR) treatment on the duration and severity of neurological symptoms of acute experimental allergic encephalomyelitis (EAE), an animal model for demyelinating diseases, particularly multiple sclerosis. To mimic the clinical situation, BCR treatment was started after the onset of clinical signs. Furthermore, the effect of BCR treatment on the course of a chronic relapsing form of EAE was studied. BCR was injected at daily intervals in a dose that resulted in sustained suppression of plasma concentrations of prolactin, a pituitary hormone that plays a role in immunoregulation. In acute EAE, BCR therapy reduced both severity and duration of the clinical signs. In chronic relapsing EAE, BCR treatment did not affect the severity and duration of the first attack, but reduced the duration of the subsequent, second attack. Thus, BCR treatment improves the clinical course in animals with ongoing disease. These findings may have implications for the search for new therapeutic approaches in multiple sclerosis.

Elimination of blood-derived macrophages inhibits the release of interleukin-1 and the entry of leukocytes into the cerebrospinal fluid in experimental pneumococcal meningitis

Parameters of inflammation during pneumococcal meningitis were determined in rabbits after monocyte elimination by dichloromethylene diphosphonate (Cl(2)MDP)-containing mannosylated liposomes in comparison with untreated controls. Monocyte depletion reduced the migration of white blood cells into the cerebrospinal fluid (CSF) (medians: 42 versus 2146/mm3 at 18 h, 323 versus 7413/mm3 at 24 h p.i., p < 0.01). CSF IL-1beta concentrations were lower in depleted animals (379 versus 3282 pg/ml, 24 h p.i., p < 0.01), whereas TNF-alpha concentrations were not different. Monocyte-depleted animals lost body temperature during the experiment carried out in anaesthesia (p = 0.01) indicating that macrophages are necessary for thermogenesis during meningitis.

Circulating macrophages as pathological effector cells after spinal cord injury

155 Circulating Maerophages as Pathological Effeetor Cells after Spinal Cord injury P.G, Popovieh. D. Hawkins, The Ohio State University College of Medicine and Public Health, Ohio, USA, I. Huitinga, N. van Rooijen, The Vrije Universiteit, Amsterdam, The Netherlands, B.T. Stokes, The Ohio State University College ofMedicine and Public Health, Ohio, USA 158 Cloning of New Genes Induced by Complement Activation in Oligodendroeytes T. Badea, F. Nienleseu, M.L. Shin, H. Pus, University of Marylund, School of Medicine, USA

Suppression of experimental allergic encephalomyelitis by treatment with catalase

During experimental allergic encephalomyelitis (EAE), large perivascular infiltrates are present in the central nervous system. These infiltrates consist for 50% of macrophages (m~b). The importance of these m~b in the pathogenesis of the disease has been shown in a study in which elimination of m~b was found to suppress the clinical signs [1]. The infiltrating m~b can secrete numerous factors, among which are the reactive oxygen species (ROS) that can cause severe tissue damage. Stimulated m~b produce ROS in a so-called respiratory burst in which oxygen is reduced to superoxide and subsequently to hydrogen peroxide and hy221

Immunohisto- and cytochemical characterization of brain macrophages and neuroglial cells in multiple sclerosis

A SUBPOPULATION OF HUMAN ASTROOLIA EXPRESSES RECEPTOR FOR COLONY ~TIMULATING FACTOR-1 (CSF-1R) WHICH IS ENCODED BY c-fins IFedoroff, S., lAhmed, I., 2yong, V.W., 3Guilbert, L. and 2Antel, J . IDepartment of Anatomy, University of Saskatchewan, 2Montreal Neurological Insti~.ute, McGill University, and 3Department of Immunology, University of Alberta, Canada. The receptor for colony stimulating factor-l(CSF-1R) is usually expressed in macrophages and their immediate precursor cells and is encoded by c-fm~. Recently it has been reported that mouse astroglia secrete CSF-1 in culture and that mouse microglia derived ~¢rom these astroglia cultures have a functional receptor for CSF-~ (Hao et al., J. Neurosci. Res. 27:314-323, 1990). We now report that human GFAP + astroglia also can express CSF-1R. Human adult and embryonic (El9 week) astroglia were cultured on coverslips and doublelabeled with antibodies to GFAP (DAKO) and to CSF-1R (Oncogene Science). Approximately 40 per cent of the astroglia expressed both GFAP and CSF-1R, indicating that a subpopulation of GFAP + astoglia expresses CSF-1R on the same ceil. That these CSF-1R are functional was indicated by their ability to specifically bind 12sI-CSF-I. When astroglia were cultured in the presence of human CSF-1, the CSF-1R could not be detected, probably indicating that it was down-regulated. Functional CSF1R on astroglia provides a means for paracrine or autocrin¢ induced asL, ceyte proliferation. Mutations or rearragements in c-fms coding sequen.~es in eztroglia could lead to aberrant proliferative responses and even neoplastic transformation. The authors are members of the Canadian Centre of Excellence in Neural Regeneration and Functional Recovery.