Published online before print August 17, 2004

This Article Full Text (Reprint (PDF)) All Versions of this Article: jlb.0604346v1 76/5/971    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Longacre, A. Articles by Levine, J. S. Search for Related Content PubMed PubMed Citation Articles by Longacre, A. Articles by Levine, J. S.

© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0604346

Received for publication June 17, 2004.
Revised July 12, 2004.
Accepted for publication July 19, 2004.

Article

Macrophages from lupus-prone MRL mice are characterized by abnormalities in Rho activity, cytoskeletal organization, and adhesiveness to extracellular matrix proteins

Section of Nephrology, Department of Medicine, The University of Illinois at Chicago

^@ To whom correspondence should be addressed. E-mail: jslevine{at}uic.edu.

Abstract

Macrophages (m) from prediseased mice of the major murine models of lupus have an identical defect in cytokine expression that is triggered by serum and/or apoptotic cells. It is striking that cytokine expression in the absence of serum and apoptotic cells is equivalent to that of nonautoimmune mice. Here, we show that m from prediseased lupus-prone MRL/MpJ (MRL/+) or MRL/MpJ-Tnfrsf6^lpr (MRL/lpr) mice also have reversible abnormalities in morphology, cytoskeletal organization, and adhesive properties. In the presence of serum, MRL m adhered in increased numbers to a variety of extracellular matrix proteins compared with m from two nonautoimmune strains. However, in the absence of serum, adhesion by MRL m was similar to that of nonautoimmune m. Increased adhesion by MRL m was also observed in the presence of apoptotic but not necrotic cells. The morphology and actin-staining pattern of adherent MRL m were consistent with reduced activity of Rho, a cytoskeletal regulator. Indeed, MRL m cultured in the presence of serum had markedly decreased levels of active Rho compared with nonautoimmune m. It is remarkable that when cultured in the absence of serum, MRL m displayed normal Rho activity and cytoskeletal morphology. Addition of a Rho inhibitor to normal m reproduced the morphologic and cytoskeletal abnormalities observed in MRL m. Taken together, our findings support the hypothesis that m from MRL and other systemic lupus erythematosus-prone mice have an apoptotic, cell-dependent, autoimmune phenotype that affects a broad range of m functions, including cytokine gene expression and Rho-dependent cytoskeletal regulation.

Key Words: rodent • autoimmunity

This article has been cited by other articles:

				V. A. Patel, A. Longacre, K. Hsiao, H. Fan, F. Meng, J. E. Mitchell, J. Rauch, D. S. Ucker, and J. S. Levine Apoptotic Cells, at All Stages of the Death Process, Trigger Characteristic Signaling Events That Are Divergent from and Dominant over Those Triggered by Necrotic Cells: IMPLICATIONS FOR THE DELAYED CLEARANCE MODEL OF AUTOIMMUNITY J. Biol. Chem., February 24, 2006; 281(8): 4663 - 4670. [Abstract] [Full Text] [PDF]

				H. Fan, V. A. Patel, A. Longacre, and J. S. Levine Abnormal regulation of the cytoskeletal regulator Rho typifies macrophages of the major murine models of spontaneous autoimmunity J. Leukoc. Biol., January 1, 2006; 79(1): 155 - 165. [Abstract] [Full Text] [PDF]