|
Lupus Meeting News: Not Just Dust: Microparticles Suspected of Role in Lupus |
SHANGHAI, China—Microparticles are elevated in the blood of patients with systemic lupus erythematosus (SLE) and may act as important mediators of autoimmunity and inflammation, Steffen Gay, MD, will report at this week’s 8th International Congress on SLE.1
May 22, 2007
by Janis Kelly
Dr. Gay is with the WHO Collaborating Center for molecular biology and novel strategies for the treatment of rheumatic diseases, at University Hospital, in Zurich, Switzerland.
“It is obvious that microparticles, previously considered to reflect some inert cellular debris or cellular ‘dust,’ have emerged as pivotal messengers for intercellular communication.”—Steffen Gay, MD.“It is obvious that microparticles, previously considered to reflect some inert cellular debris or cellular ‘dust,’ have emerged as pivotal messengers for intercellular communication,” Dr. Gay says.
Left behind after inflammation, apoptosis
Microparticles are small membrane-coated vesicles shed from plasma membrane following stimulation by pro-inflammatory mediators or during the early stages of apoptosis. “Although these particles are at present only largely defined by structural features, they appear to act as powerful subcellular elements involved in cell signalling [and] initiation of gene expression, [and are] thereby novel modulators of cellular communication,” Dr. Gay explains.
Microparticles derived from T-cells and monocytes induce synthesis of a number of inflammatory mediators such as interleukins-6 and -8, and a number of chemokines such as monocyte chemoattractant proteins 1 and 2 (MCP-1, MCP-2.) These particles also induce the synthesis of matrix-degrading enzymes, such as matrix metalloproteinases-1, -3, -9, and -13 (MMP-1, MMP-3, MMP-9, and MMP-13.)
Dr. Gay points out that microparticles might induce inflammatory mediators in immune cells and facilitate migration of these cells through the extracellular matrix. His research indicates that microparticles disturb lipid homeostasis and trigger apoptosis in macrophages, which led him to study microparticles in SLE and apoptosis abnormalities.
“In a collaborative study between Semmelweis University, in Budapest, Hungary, and our laboratory we searched for the presence of microparticles in the blood of patients with SLE and explored the role of apoptosis in immune cells. The levels of microparticles derived from B-lymphocytes and monocytes, but not from T-cells, were found to be elevated in the serum of SLE patients when compared to healthy controls matched for age and gender,” Dr. Gay reports. Adding the microparticles to isolated T-cells from the SLE patients induced dose-dependent proliferation and reduced T-cell apoptosis. This effect did not occur in cells from normal subjects.
Dr. Gay concludes that microparticles “may act as novel important mediators of autoimmunity and inflammation.”
