Biology Reference
In-Depth Information
their inflammatory recruitment and activation during the course of
infection [86] is well appreciated. Very little is known, however, about
the distribution of complement components in early hematopoietic
progenitor cells, their potential role in hematopoietic development,
and the complement-mediated interactions that influence the homing
of lymphoid progenitors to various tissues.
In this respect, a recent study has demonstrated that the G-protein-
coupled receptors for both C3a and C5a anaphylatoxins are expressed
by human clonogeneic CD34
+
cells, and that both complement compo-
nents C3 and C5 are locally synthesized by the bone marrow stroma
[87]. In addition, stimulation of the C3a receptor (C3aR) appears to reg-
ulate the chemotaxis of human CD34
+
cells by synergistically
increasing the migration of these cells in the presence of
a
-chemokine
stromal-derived factor-1 (SDF-1). Moreover, C3a has been shown to
modulate various homing activities of stem cells by increasing their
sensitivity to low doses of SDF-1 [87,88]. These striking observations
have laid the groundwork for further investigation of the hypothesis
that a functional cross-talk between the C3aR and CXCR4 signaling
pathways may play an important role in the homing of human
stem/progenitor cells to the bone marrow hematopoietic niches.
Corroborating this hypothesis, recent studies have shown that
C3a and its receptor C3aR promote the retention of hematopoietic
progenitor/stem cells in the bone marrow during stem cell mobiliza-
tion in mice [89]. C3
mice exhibit increased release
of bone marrow progenitors into circulation following GCSF-induced
mobilization. Furthermore, mice treated with a specific C3aR antago-
nist show accelerated mobilization of hematopoitic stem cells
(HSC) to the periphery, suggesting that antagonists of the C3aR can
potentially serve as mobilizing agents for HSC transplantation
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A Novel Bioinformatics Platform for Text-Based Knowledge Discovery
and “Mining” of Complement-Related “Systems” Associations
Biomolecular (structural and sequence) data generated by means of
high-throughput screening techniques play an integral role in the gen-
eration of new biomedical knowledge and in the interpretation of
complex biological systems. However, this enormous growth of exper-
imental data has led to a reciprocal increase of the volume of scientific
literature available in the databases. In this respect, researchers are now
faced with the ultimate challenge of integrating both experimental and
textual information in order to create a comprehensive context for
interpreting and predicting gene and pathway associations and also
generating new knowledge in a systematic, hypothesis-driven way.
New text-mining algorithms are being developed in an effort to enable
scientists to efficiently extract biological information from text databases,
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