More MS news articles for Nov 2001

CCR1+/CCR5+ Mononuclear Phagocytes Accumulate in the Central Nervous System of Patients with Multiple Sclerosis

Am J Pathol 2001 Nov;159(5):1701-1710
Trebst C, Lykke Sorensen T, Kivisakk P, Cathcart MK, Hesselgesser J, Horuk R, Sellebjerg F, Lassmann H, Ransohoff RM.
Departments of Neurosciences and Cell Biology, the Lerner Research Institute, the Cleveland Clinic Foundation, Cleveland, Ohio. the Mellen Center for Multiple Sclerosis Treatment and Research, The Cleveland Clinic Foundation, Cleveland, Ohio. University of Copenhagen, Glostrup Hospital, Glostrup, Denmark. Richmond, California. University of Vienna, Vienna, Austria.

Mononuclear phagocytes (monocytes, macrophages, and microglia) are considered central to multiple sclerosis (MS) pathogenesis.

Molecular cues that mediate mononuclear phagocyte accumulation and activation in the central nervous system (CNS) of MS patients may include chemokines RANTES/CCL5 and macrophage inflammatory protein-1alpha/CCL3.

We analyzed expression of CCR1 and CCR5, the monocyte receptors for these chemokines, on circulating and cerebrospinal fluid CD14+ cells, and in MS brain lesions.

Approximately 70% of cerebrospinal fluid monocytes were CCR1+/CCR5+, regardless of the presence of CNS pathology, compared to less than 20% of circulating monocytes.

In active MS lesions CCR1+/CCR5+ monocytes were found in perivascular cell cuffs and at the demyelinating edges of evolving lesions.

Mononuclear phagocytes in early demyelinating stages comprised CCR1+/CCR5+ hematogenous monocytes and CCR1-/CCR5- resident microglial cells.

In later stages, phagocytic macrophages were uniformly CCR1-/CCR5+. Cultured in vitro, adherent monocytes/macrophages up-regulated CCR5 and down-regulated CCR1 expression, compared to freshly-isolated monocytes.

Taken together, these findings suggest that monocytes competent to enter the CNS compartment derive from a minority CCR1+/CCR5+ population in the circulating pool.

In the presence of ligand, these cells will be retained in the CNS.

During further activation in lesions, infiltrating monocytes down-regulate CCR1 but not CCR5, whereas microglia up-regulate CCR5.

PMID: 11696431 [PubMed - as supplied by publisher]