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19 April 2014 : Research paper  

Calreticulin contributes to C1q-dependent recruitment of microglia in the leech Hirudo medicinalis following a CNS injury

Francoise Le Marrec-CroqDEF, Annelise Bocquet-GarconBCD, Jacopo VizioliBCD, Christelle VancampAB, Francesco DragoAB, Julien FranckBC, Maxence WisztorskiBC, Michel SalzetFG, Pierre-Eric SautiereDEF, Christophe LefebvreDEFG

DOI: 10.12659/MSM.890091

Med Sci Monit 2014; 20:644-653

Abstract

BACKGROUND: The medicinal leech is considered as a complementary and appropriate model to study immune functions in the central nervous system (CNS). In a context in which an injured leech’s CNS can naturally restore normal synaptic connections, the accumulation of microglia (immune cells of the CNS that are exclusively resident in leeches) has been shown to be essential at the lesion to engage the axonal sprouting. HmC1q (Hm for Hirudo medicinalis) possesses chemotactic properties that are important in the microglial cell recruitment by recognizing at least a C1q binding protein (HmC1qBP alias gC1qR).

MATERIAL AND METHODS: Recombinant forms of C1q were used in affinity purification and in vitro chemotaxis assays. Anti-calreticulin antibodies were used to neutralize C1q-mediated chemotaxis and locate the production of calreticulin in leech CNS.

RESULTS: A newly characterized leech calreticulin (HmCalR) has been shown to interact with C1q and participate to the HmC1q-dependent microglia accumulation. HmCalR, which has been detected in only some microglial cells, is consequently a second binding protein for HmC1q, allowing the chemoattraction of resident microglia in the nerve repair process.

CONCLUSIONS: These data give new insight into calreticulin/C1q interaction in an immune function of neuroprotection, suggesting another molecular target to use in investigation of microglia reactivity in a model of CNS injury.

Keywords: Amino Acid Sequence, Base Sequence, Biotinylation, Calreticulin - metabolism, Central Nervous System - pathology, Chemotaxis, Complement C1q - metabolism, Hirudo medicinalis - metabolism, Microglia - pathology, Molecular Sequence Data, Phylogeny, Protein Binding, RNA, Messenger - metabolism, Solubility

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750