Interactions between cytokines and a2-macroglobulin
Department of Surgery, University of Edinburgh, Teviot
Place, Edinburgh, UK
Immunology Today 1990: Vol. 11, No. 5, pp. 163-166
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