Induction of ICAM-1 on human neural cells and mechanisms of neutrophil-mediated injury.
To define mechanisms by which inflammatory cells damage neural tissue, the author investigated stimuli that promote leukocyte adherence and injury to cultured human cortical neuron (HCN-1) and neuroblastoma cells (LAN-1 and SK-N-SH). Neutrophils do not adhere to unstimulated neural cells but will bind to neural cells that have been exposed to tumor necrosis factor alpha (TNF alpha) and in some cases other cytokines such as gamma interferon (gamma IFN) or interleukin-1 (IL-1). Tumor necrosis factor alpha induces synthesis of intercellular adhesion molecule-1 (ICAM-1) mRNA and cell surface expression of ICAM-1 on cultured neural cells. Adherence of neutrophils to cytokine-stimulated neural cells is mediated primarily by ICAM-1:LFA-1 interactions, because 70% to 90% of the binding can be blocked by monoclonal antibodies to either ligand. Prior introduction of an oxidizable dye, 5-(and 6-)carboxy-2',7' dichlorofluorescin diacetate into the LAN-1 cells demonstrates that adherent neutrophils can release oxidizing radicals into the neural cell cytoplasm. These results suggest that cytokines released in the course of inflammation may induce expression of ICAM-1 on neurons, allowing them to be targeted by leukocytes expressing the appropriate receptors. The resulting adhesive interactions may facilitate introduction of various toxic agents into the neural cytoplasm.
Department of Otolaryngology, Baylor College of Medicine, Houston, TX 77030.
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Birdsall
D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D005609:Free Radicals; D006801:Humans; D018799:Intercellular Adhesion Molecule-1; D007962:Leukocytes / Q000502:physiology; D009447:Neuroblastoma / Q000378:metabolism* / Q000473:pathology; D009474:Neurons / Q000378:metabolism*; D009504:Neutrophils / Q000502:physiology*; D016877:Oxidants / Q000378:metabolism; D014407:Tumor Cells, Cultured
D015815:Cell Adhesion Molecules; D005609:Free Radicals; D016877:Oxidants; D018799:Intercellular Adhesion Molecule-1