Activation of microglia: a neuroinflammatory role for CAP37.
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.
Pereira
H Anne
HA
Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City 73104, USA. anne-pereira@ouhsc.edu
Ruan
Xin
X
Kumar
Padmasini
P
D000818:Animals; D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins / Q000494:pharmacology / Q000502:physiology*; D002352:Carrier Proteins / Q000494:pharmacology / Q000502:physiology*; D002460:Cell Line; D018925:Chemokines / Q000096:biosynthesis; D002633:Chemotaxis / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D018836:Inflammation Mediators / Q000494:pharmacology / Q000502:physiology*; D051379:Mice; D017628:Microglia / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D010587:Phagocytosis / Q000187:drug effects
C062991:AZU1 protein, human; D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins; D002352:Carrier Proteins; D018925:Chemokines; D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D018836:Inflammation Mediators