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Interactions between cytokines and a2-macroglobulin

James K.

Department of Surgery, University of Edinburgh, Teviot Place, Edinburgh, UK

Immunology Today 1990: Vol. 11, No. 5, pp. 163-166

402 KA

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Cytokines are often thought of as short range, short half-life molecules. This view may now be challenged by recent findings that indicate that a2-macroglobulin and antibodies to cytokines may alter cytokine kinetics in vivo. a2-Macroglobulin, one of the major proteins in serum, can bind a wide range of physiologically important molecules. As Keith James reviews here, the interaction between a2-macroglobulin and a number of cytokines has recently come under scrutiny, revealing a new and potentially important mechanism for the modulation of cytokine activity, while in the following paper a modulatory role for anti-cytokine antibodies is considered.

 The rapid progress in the cloning and expression of cytokine genes during recent years, coupled with advances in their purification and characterization, has generated considerable academic and commercial interest, in addition to increasing knowledge of normal and pathophysiological processes, it has offered new opportunities for the treatment of a wide variety of clinical conditions including cancer, autoimmune and infectious diseases and haematological disorders. The biological effects of these products are undoubtedly influenced by their interaction with other molecules, particularly in vivo. The extent and possible significance of such interaction, with respect to interleukin 1 (IL-1), has recently been reviewed1. However, it is perhaps not widely appreciated that evidence has emerged during recent years to indicate that one of the major serum proteins, namely a2-macroglobulin, interacts with, and sometimes modifies, the properties of a wide range of cytokines2-10. These recent studies confirm earlier observations performed with less highly purified materials, which indicated that a2-macroglobulin bound macrophage-activating factor11 and nerve growth factor12.

 The steadily increasing number of reports on the interaction of cytokines with a2-macroglobulin are of interest for a variety of reasons. First, they may help explain some of the immunological and growth promoting properties previously ascribed to a2-macroglobulin (reviewed in Ref. 13). Furthermore, they could be extremely relevant to the assay, mode of action and therapeutic application of this increasingly important group of molecules. In this brief article, the basic properties of a2-macroglobulin will be presented with special emphasis on its interaction with cytokines and their possible immunological significance.

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