Alpha2-macroglobulin is a novel substrate for ADAMTS-4 and ADAMTS-5 and represents an endogenous inhibitor of these enzymes.

Osteoarthritis is characterized by the loss of aggrecan and collagen from the cartilage extracellular matrix. The proteinases responsible for the breakdown of cartilage aggrecan include ADAMTS-4 (aggrecanase 1) and ADAMTS-5 (aggrecanase 2). Post-translational inhibition of ADAMTS-4/-5 activity may be important for maintaining normal homeostasis of aggrecan metabolism, and thus, any disruption to this inhibition could lead to accelerated aggrecan breakdown.

Human CD46 enhances nitric oxide production in mouse macrophages in response to measles virus infection in the presence of gamma interferon: dependence on the CD46 cytoplasmic domains.

CD46 is a transmembrane complement regulatory protein widely expressed on nucleated human cells. Laboratory-adapted strains of measles virus (MV) bind to the extracellular domains of CD46 to enter human cells. The cytoplasmic portion of CD46 consists of a common juxtamembrane region and different distal sequences called Cyt1 and Cyt2.

Expression of human complement regulatory protein CD46 restricts measles virus replication in mouse macrophages.

Measles virus (MV) can infect mouse macrophages to cause a prolonged non-cytopathic infection that produces low levels of infectious virus for days. We have generated RAW264.7 mouse macrophages expressing human CD46, a cell surface complement regulatory protein that serves as a receptor for laboratory-adapted strains of MV.

The cytoplasmic domains of complement regulatory protein CD46 interact with multiple kinases in macrophages.

Membrane cofactor protein (CD46), which normally protects autologous cells from complement lysis, is the human cell receptor for measles virus (MV). Interaction between MV and CD46 on monocytes can lead to suppression of monocyte activation. We have investigated the interaction between the cytoplasmic sequences of CD46 and kinases in a mouse macrophage cell line.

Human cell receptor CD46 is down regulated through recognition of a membrane-proximal region of the cytoplasmic domain in persistent measles virus infection.

Monkey cells persistently infected by measles virus (MV) Biken strain (Biken-CV-1 cells) showed no cytopathic effects and lacked surface expression of a homolog of human cell receptor, membrane cofactor protein CD46. Transfection of a human CD46 gene into these cells induced extensive cell fusion, indicating that down regulation of the endogenous CD46 homolog was essential for the maintenance of a noncytopathic mode of infection. Surface expression of the exogenously introduced human CD46 was also drastically down regulated in the persistently infected cells compared with uninfected cells.