Activation of microglia: A neuroinflammatory role for CAP37

Abstract

Recent evidence suggests that inflammation and immune function in the central nervous system (CNS) may play a considerable role in the progression of many neurodegenerative diseases. It is known that microglia, the CNS equivalent of peripheral blood monocytes, may be instrumental in causing neurotoxicity. However, the mediator(s) that activates microglia to produce toxic substances that orchestrate cell death has yet to be elucidated. We have identified a novel inflammatory molecule, cationic antimicrobial protein of molecular weight 37 kDa (CAP37), to the brains of patients dying from Alzheimer's disease. CAP37 is known to be a potent activator and regulator of monocyte function in the systemic circulation. We hypothesize that CAP37, a mediator previously shown to recruit and activate monocytes in the systemic circulation, may also play a role in CNS inflammation by modulating microglial function. Here we demonstrate that CAP37 is a chemoattractant for microglia and that CAP37-treated microglia express class II major histocompatibility antigens and produce proinflammatory cytokines and chemokines. We conclude that CAP37 has the ability to activate microglial cells and suggest that it has the potential to serve as a neuroinflammatory molecule. GLIA 41:64 -72, 2003.

Neutrophil primary granule proteins HBP and HNP1–3 boost bacterial phagocytosis by human and murine macrophages

“…Thus, HBP has to act directly on the macrophages as indicated by a rapid Ca 2+ mobilization. In line with the mechanism proposed by our data, an enhanced phagocytosis of zymosan by microglial cells in response to HBP was recently shown (33). This response was associated with enhanced expression of MHC class II (33), which is in agreement with the upregulation of HLA class II in our study.…”

“…In line with the mechanism proposed by our data, an enhanced phagocytosis of zymosan by microglial cells in response to HBP was recently shown (33). This response was associated with enhanced expression of MHC class II (33), which is in agreement with the upregulation of HLA class II in our study. The significance of our finding is further highlighted by observations in a murine disease model, in which it is reported that i.p.…”

Neutrophil-derived azurocidin alarms the immune system

“…Treatment of macrophages with azurocidin enhanced the expression of HLA II, CD40, and CD86, in agreement with findings from microglial cells treated similarly [45]. Expression of these molecules is a sign of the classical macrophage activation being functionally related to enhanced antimicrobial effectiveness and a more powerful activation of the adaptive immune system [46].…”

Neutrophil granule proteins tune monocytic cell function

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