Hungarian Immunology

[Relevances of anti-CD44 immunotherapy for cellular biology]

GÁL István, GLANT T. Tibor, MIKECZ Katalin

MARCH 20, 2002

Hungarian Immunology - 2002;1(01)

[INTRODUCTION - The CD44 molecule - the physiologic hialuronic acid receptor - is one of key mediators that direct the traffic of leukocytes into inflamed tissues. When applied in animal models of autoimmune arthritis, parenteral anti-CD44 antibody treatment exerts a dramatic antiinflammatory effect, but at high doses also a leukopenic effect. The goal of the present work is to elucidate the cellular basis of these phenomena. METHODS - In this study the authors used Western blot, immunoprecipitation, cell adhesion studies, flow chamber system studies (leukocyte rolling) and fluorescence microscopy following fluorescent labeling of actin cytoskeleton. RESULTS - Adhesion of CD44-expressing leukocytes to immobilized hialuronic acid does not result marked changes in cellular morphology. When incubated on immobilized anti-CD44 antibody, however, these cells spread, reorganize the actin cytoskeleton, and they adhere strongly to the surface. Studying the mechanisms of signal transduction, the authors found that engagement of CD44 with anti- CD44 antibody results in its enhanced association with numerous cytoskeletal regulator proteins, including ezrin, ankyrin, spectrin and focal adhesion kinase, thereby increasing the interaction between the cytoskeleton and the plasma membrane. Strong adhesion of the cells to immobilized anti-CD44 also prevents the rolling movement of these cells, mediated by CD44-hialuronic acid interactions, which precedes the extravasation of leukocytes to sites of inflammation. CONCLUSION - These results may provide insight into the antiinflammatory mechanisms of anti- CD44 antibody treatment. Based on these results and results published by other investigators, anti- CD44 antibodies may be uselful in the immunotherapy of rheumatic diseases.]

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