Biology Reference
In-Depth Information
800
700
600
500
400
300
200
100
0
Figure 3.8 Chemotactic properties of conditioned media from astrocytes stimulated
with HMGB1. The conditioned media (CM, 600 l) of astrocytes, cultured for 24 hours in the
presence of the indicated concentrations of HMGB1 or CCM or LPS and a 40 nM HMGB1
solution, were placed in the bottom of a 24-well plate. Mono Mac 6 cells (100 l) were seeded
in the upper compartment of Transwell® chambers (8 m pore size) at a density of 2  10 6 /ml.
After 1.5 hours, cells on the filter were counted; data are expressed as percentage of cells that
migrated in the absence of a chemotactic stimulus. Five random fields were counted for each
duplicate sample.
Source: Ref. [46]. Copyright 2007. The American Association of Immunologists, Inc.
stimulated with 4 and 40 nM HMGB1, show a threefold and sixfold increase, respec-
tively, in chemotactic activity in comparison with the medium of unstimulated cells.
Moreover, the chemotactic activity of the conditioned medium from astrocytes
exposed to 40 nM HMGB1 was similar to that obtained upon cell exposure to the
CCM. Of note, the conditioned medium of astrocytes treated with 0.3 pg/ml LPS,
corresponding to the amount of contaminating LPS present at the maximal concen-
tration of recombinant HMGB1 utilized in this experiment, did not display chemo-
tactic activity on the monocytic cell line Mono Mac 6.
Although the complex mixture of bioactive molecules released by HMGB1-
stimulated astrocytes has not as yet been fully characterized, these results indi-
cate that it displays potent monocyte chemoattractant properties. We can speculate
that CCL2, present at high concentrations in the conditioned medium of HMGB1-
stimulated astrocytes, could also promote migration of neural progenitor cells
(NPCs), thus contributing to the neurogenesis that occurs during development of,
and throughout adult life in, the CNS [80] . Moreover, the mixture of factors released
by astrocytes stimulated with HMGB1 also contains CX 3 CL1, a chemokine able to
protect neurons from glutamate-induced toxicity [81] . Hence, the concomitant pres-
ence of CCL2 and CX 3 CL1 could exert a positive effect on neuron survival. In con-
trast, it has been reported that CCL2 is also involved in neurotoxic microglia activity
Search WWH ::




Custom Search