Upregulation in rat spinal cord microglia of the nonintegrin laminin receptor 37 kDa-LRP following activation by a traumatic lesion or peripheral injury.
The molecular mechanisms triggering microglial activation after injury to the central nervous system, involving cell-extracellular matrix interactions and cytokine signaling, are not yet fully understood. Here, we report that resident microglia in spinal cord express low levels of the non-integrin laminin receptor precursor (LRP), also found on certain neurons and glial cells in the peripheral nervous system. 37LRP/p40 and its 67-kDa isoform laminin receptor (LR) were the first high-affinity laminin binding proteins identified. While the role of laminin receptor was later attributed to integrins, LRP/LR gained new interest as receptors for prions, and their interaction with laminin seems important for migration of metastatic cancer cells. Using immunohistochemistry and Western blotting, we demonstrate that traumatic spinal cord injury leads to a strong and rapid increase in LRP levels in relation to activated microglia/macrophages. Associated with laminin re-expression in the lesion epicenter, LRP-positive microglia/macrophages exhibit a rounded, ameboid-like shape characteristic of phagocytic cells, whereas in more distant loci they reveal a hypertrophied cell body and short ramifications. The same morphological difference is observed in vitro for purified microglia cultured with or without laminin. Strong, transient upregulation of LRP by activated spinal cord microglia is also induced by transection of the sciatic nerve that affects the spinal cord circuitry without blood-brain barrier dysruption. LRP expression is maximal by 1 week post-lesion, before becoming restricted to dorsal and ventral horns, sites of major structural reorganization. Our findings strongly suggest the involvement of LRP in lesion-induced activation and migration of microglia.
Baloui
Hasna
H
Université Pierre et Marie Curie-Paris6, UMR7101 NSI; and CNRS, UMR7101 IFR-83, Paris, France.
Stettler
Olivier
O
Weiss
Stefan
S
Nothias
Fatiha
F
von Boxberg
Ysander
Y
D000354:Africa, Western; D000367:Age Factors; D000818:Animals; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D005260:Female; D007536:Isomerism; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D017628:Microglia / Q000166:cytology / Q000378:metabolism*; D011498:Protein Precursors / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012269:Ribosomal Proteins / Q000737:chemistry / Q000378:metabolism*; D012583:Schwann Cells / Q000166:cytology; D012584:Sciatic Nerve / Q000378:metabolism / Q000473:pathology; D020426:Sciatic Neuropathy / Q000378:metabolism* / Q000473:pathology; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology; D013119:Spinal Cord Injuries / Q000378:metabolism* / Q000473:pathology; D015854:Up-Regulation / Q000502:physiology
D011498:Protein Precursors; D012269:Ribosomal Proteins; C086117:Rpsa protein, rat