Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P05109 (S100A8)
 1,212 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Microglial cells are regulators of tissue homeostasis in the adult central nervous system and readily participate in pathological processes, orchestrating tissue remodeling. Cytokines produced by microglial cells are markers of cell activation and contribute to reactive processes. In this paper, we have studied the expression of IL-16 (leukocyte chemoattractant factor), a natural soluble ligand to the CD4 molecule, in human fetal brains from the 11th to the 20th(.) week of gestation by immunohistochemistry. Interleukin (IL)-16(+) cells were detected already at the 11th gestational week, accumulating with aging in cortical layers (P<0.0001) at the 16th and 19th week, and reaching maximum numbers in the 20th week. Most IL-16(+) microglia (>80%) revealed morphological hallmarks of activated microglia. We observed that IL-16 cells coexpress LCA (>80%) and MRP-8, an activation-associated Ca(2+) binding S-100 family member (>80%). In contrast, only few IL-16(+) cells proliferated (PCNA(+), 20-40%) or co-expressed the HLA-DR, -DP, or -DQ antigen (<10%), and rare coexpression with CD68 (20-40%) was detected until 17th week. No coexpression with CD4, CD8 or CD20 was detected. Furthermore, we observed accumulation of IL-16(+) microglia in zones of neuronal proliferation, migration and differentiation. Increasing numbers of IL-16(+) cells were detected in bordering zones adjacent to the basal ganglia. Our data suggests that the early presence of IL-16(+) microglia exert a CD4-independent function-mediating activation, and chemotaxis of microglia precursors during neuronal development. In addition, IL-16 immunoreactivity might be a helpful tool to determine distinct developmental stages of microglial cells during fetal central nervous system ontogeny.
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PMID:IL-16 is differentially expressed in the developing human fetal brain by microglial cells in zones of neuropoesis. 1122 58

Focal cerebral ischemia elicits a strong inflammatory response which readily participates in lipid oxygenation, edema formation, apoptotic cell death and tissue remodeling. Within these conditions, cytokines are key players of cell activation and are crucial for delayed mechanisms of ischemic damage. Mature IL-16 is an immunomodulatory cytokine, exerting CD4 dependent and independent effects and is characterized by chemotactic activity, induction of early gene phosphorylation, stimulation of pro-inflammatory IL-1beta, IL-6, TNFalpha expression in monocytic cells and also modulates apoptosis. We have now analyzed expression of IL-16 in 20 brains of patients following focal cerebral infarctions (FCI, n=20). Compared to normal control brains (n=3), IL-16 was expressed by infiltrating immune cells such as neutrophils, CD8+ lymphocytes and activated CD68+ microglia/macrophages accumulating in lesion associated reactive zones and in peri-vascular regions. IL-16+ cells accumulated significantly (P<0.0001) in the necrotic lesion and at bordering peri-lesional areas at day 1-2 reaching maximum levels at day 3-4 (P<0.0001). Also, peri-vascular IL-16+ cells reached maximum levels at day 3-4 (P<0.0001) following infarction and decreased after several weeks. During the early microglial activation period, IL-16+ microglia/macrophages coexpress the activation antigen MRP-8. The accumulation of IL-16+ granulocytes, IL-16+, CD8+ lymphocytes and activated IL-16+, CD68+, CD4- microglia/macrophages, early after infarction suggest a CD4 independent, paracrine role of IL-16 in the postinjury inflammatory response, such as recruitment and activation of immune cells leading to microvessel clustering and blood-brain barrier disturbance resulting in secondary damage.
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PMID:Human focal cerebral infarctions induce differential lesional interleukin-16 (IL-16) expression confined to infiltrating granulocytes, CD8+ T-lymphocytes and activated microglia/macrophages. 1124 37

Following surgical removal of glioblastoma multiforme (GBM), radiochemotherapy impedes neoplastic outgrowth and relapse formation. Macrophages/microglial cells are believed to be potent mediators of the host defense system in GBM. However, little is known about their alteration by postsurgical therapies. We have now analyzed expression of LCA (leucocyte common antigen), CD68 (phagocytic cells), HLA-DR, -DP, -DQ (MHC class II), MRP-8 (myeloid-related protein, S100A8), MRP-14 (S100A9), LCF (lymphocyte chemoattractant factor, IL-16) and NOS II (inducible nitric oxide synthase) in macrophages/microglial cells in 39 GBM relapses and their matched primary tumors. Following surgery of the primary tumors, 15 patients received irradiation and chemotherapy, 17 irradiation and 7 no treatment. In irradiated relapses, we observed significantly more macrophages/microglial cells expressing MRP-14 compared to untreated GBM relapses. Furthermore, we observed a significant increase of CD68 expressing macrophages/microglial cells in patients without postsurgical treatment, but not in those with radiochemotherapy. In conclusion, our findings suggest that radiochemotherapy alters the number of MRP-14 expressing cells. The lacking increase of CD68 expressing cells in patients with radiochemotherapy suggests depletion of this cell type by postsurgical therapy.
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PMID:Macrophage/microglial cell subpopulations in glioblastoma multiforme relapses are differentially altered by radiochemotherapy. 1185 68

As the primary intrinsic immune effector cells of the central nervous system, microglia are involved in virtually all pathological processes of the brain and spinal cord including inflammatory, neurodegenerative, traumatic, neoplastic and vascular diseases. Despite this important role, there is a lack of data concerning microglial distribution and protein expression in the human spinal cord. In this study, we immunohistochemically investigated 10 normal human spinal cords to establish reference data and compared these results with 15 pathological human spinal cords deriving from distinct pathologies. Each spinal cord was evaluated at eight different levels for three white and two grey matter areas for both constitutive (MHC-II, CD68, IL-16, AIF-1, LCA, CD4) and reactive (MRP-8, MRP-14) microglial antigens. Whereas previous studies revealed significant regional differences in microglial distribution and protein expression in human brain, normal spinal cord displayed a uniform expression pattern, reaching levels of up to 17% MHC-II positive cells of the total cell population. This datum formed the basis for the further evaluation of microglia expression levels in pathological spinal cords, where levels of up to 45% positive cells were observed. Our results represent important reference values for future neuropathological diagnostic and therapeutical approaches in spinal cord pathologies.
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PMID:Differential microglial regulation in the human spinal cord under normal and pathological conditions. 1708 79