Cell Growth in Microgravity
311
4.1
Signal Transduction in Microgravity
An important phase of the microgravity-
induced perturbations in transmembrane
signaling is selective and not random.
Most cells adapt to the new signal motifs
and are able to survive. Several studies,
beginning with Spacelab D-1 in 1985,
SLS-1 in 1991, IML-1 in 1992, IML-2 in
1994, STS-55, -56, and many sounding
rocket experiments from the mid-1980s to
the mid-1990s, attest to the ability of cells
to adapt to change induced by microgravity
environments. The flight experiments, and
ground-based studies using microgravity
analog culture, suggest that single cells
are sensitive to changes in gravity, as
reflected by proliferation, gene expression,
locomotion, and receptor-mediated signal
transduction and differentiation.
Mammalian immune performance is
critically tied to the function of thymus-
dependent (T) lymphocytes. A hallmark of
immune performance is the response of
T-lymphocytes to activation through cell-
surface receptors. The Frst
in vitro
T-cell
activation experiments were performed
aboard Spacelab 1 in 1983 by Cogoli et al.
(Table 1). Results showed a dramatic sup-
pression of T-cell activation in response
to the widely used polyclonal activator,
Concanavalin A. Spacelab D1 in 1985
and Spacelab SLS1 in 1991 continued the
investigation of T-lymphocytes. The exper-
iments conFrmed the inhibition of T-cell
activation in microgravity and raised the
possibility of direct and indirect effects
of gravity unloading on the T cells. The
Frst signal required for T-cell activation is
the presentation of antigen by the antigen-
presenting cell, which activates a G-protein
and phospholipase C. In the SLS-1 flight,
it was found that production of the cy-
tokine interleukin 1 (IL-1) expression was
impaired in the monocytes. Interleukin-1
is a second signal that is necessary for T-
cell activation. The subsequent signal to
achieve full T-cell activation is the synthe-
sis of the cytokine Interleukin 2 (IL-2) and
the expression of its receptor (IL-2R). The
Frst signal of antigen presentation is mod-
eled
in vitro
using Concanavalin A (a plant
lectin) that binds to saccharide groups on
the T-cell antigen receptor. An interest-
ing observation from this study was that
the binding of Concanavalin A to the cell
membrane and subsequent events, such
as capping and patching of membrane
proteins, were not altered in microgravity.
SLS-1 experiments showed that monocytes
present in the preparations flown did not
release Interleukin-1 (IL-1). Therefore, it
was hypothesized that the reason for the
inability of T cells to activate in micro-
gravity was the absence of IL-1 production
by monocytes and hence, absence of the
accessory signal. However, the production
of interferon-gamma (I±N-
γ
)wass
l
igh
t
ly
but signiFcantly restored. The receptor for
IL-2 was secreted in adequate amounts in
lymphocyte supernatants in microgravity.
Importantly, the absence of activation was
not due to a lack of cell–cell contact.
It is known that spaceflight conditions
and microgravity
per se
alters immune
function. Indeed, the altered immune
function may be the summation of the in-
dividual influence of stress (psychological
and physical), cosmic radiation, and mi-
crogravity. Thus, the space environment
may affect immune performance either
directly, because of microgravity-induced
changes or indirectly, through the stress
related to performance and conFnement.
Therefore, interpretation of spaceflight
studies on immunity must delineate the
direct and indirect effects of microgravity
on cells from the other factors associated
with spaceflight.
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