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Thrombin‐Induced Activation of Cultured Rodent Microglia
Author(s) -
Möller Thomas,
Hanisch UweKarsten,
Ransom Bruce R.
Publication year - 2000
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2000.0751539.x
Subject(s) - thrombin , hirudin , tissue factor , thrombomodulin , microglia , pertussis toxin , tumor necrosis factor alpha , chemistry , microbiology and biotechnology , biology , immunology , endocrinology , inflammation , medicine , coagulation , signal transduction , platelet , g protein
Microglia are the resident immune cells of the CNS. Upon brain damage, these cells are rapidly activated and function as tissue macrophages. The first steps in this activation still remain unclear, but it is widely believed that substances released from damaged brain tissue trigger this process. In this article, we describe the effects of the blood coagulation factor thrombin on cultured rodent microglial cells. Thrombin induced a transient Ca 2+ increase in microglial cells, which persisted in Ca 2+ ‐free media. It was blocked by thapsigargin, indicating that thrombin caused a Ca 2+ release from internal stores. Preincubation with pertussis toxin did not alter the thrombin‐induced [Ca 2+ ] i signal, whereas it was blocked by hirudin, a blocker of thrombin's proteolytic activity. Incubation with thrombin led to the production of nitric oxide and the release of the cytokines tumor necrosis factor‐α, interleukin‐6, interleukin‐12, the chemokine KC, and the soluble tumor necrosis factor‐α receptor II and had a significant proliferative effect. Our findings indicate that thrombin, a molecule that enters the brain at sites of injury, rapidly triggered microglial activation.