Cathelicidin and defensins regulate stem cell homing
Kofi
the one hand, I've been looking at SDF-1 as a factor in regenerative
medicine that could be mixed with stromal fat cells and, on the other
hand, I've been looking at cathelicidin as a vital factor in maintaining
barrier function both in the gut and in the scalp. These two areas are
both repositories for LGR5+ stem cell population and mast cells play a
role in the autoimmune conditions that affect each tissue.
Now we find out cathelidicin and beta-defensins play a role in stem cell
honing to repair damaged tissue - so this is probably an issue in
diseases as diverse as Crohn's, IBD and male-pattern baldness - all of
which are aggravated by or associated somehow with vitamin D3
deficiency. This would mean these disorders are a kind of
cathelicidin-deficiency - as I hypothesized for MPB over a year ago.
Since cathelicidin doesn't always strictly come from vitamin D3 refering
to these disorders as "cathelicidin deficiency" is more accurate than
"vitamin D deficiency."
In the gut, cathelidicin appears to regulate intestinal barrier function
directly via EGF and magnesium absorption (TRPM6) via the same EGF
pathway (which might be a reason not to drink green tea; it's an EGF
inhibitor).
In the scalp, cathelicidin is an anti-apoptotic factor for
keratinocytes. It also has angiogenic functions.
Cathelicidin is synthesized by
+ vitamin D3
+ exercise (maybe via HIF-1a)
+ butyrate (from digested fiber or possibly a ketogenic diet; requires
carnitine for absorption; males have greater natural carnitine levels
and lower rates of autoimmunity; defects in the carnitine transporter
OCTN2 seems to predispose for Crohn's; exercise, intermittent fasting
and PPARalpha agonists upregulate OCTN2; butyrate is also an epigenetic
regulator)
+ HIF-1a (lowered by iron; activated by green tea and other iron
chelators; activated by exercise).
Lgr5 stands for leucine-rich-repeat-containing G-protein-coupled
receptor. Another name for cathelicidin is leucine leucine-37 (LL-37).
What's the deal with all the leucine? Connection?
Leukemia. 2009 Aug 6;
Impaired mobilization of hematopoietic stem/progenitor cells in
C5-deficient mice supports the pivotal involvement of innate immunity in
this process and reveals novel promobilization effects of granulocytes.
Lee HM, Wu W, Wysoczynski M, Liu R, Zuba-Surma EK, Kucia M, Ratajczak J,
Ratajczak MZ.
Stem Cell Biology Program at the James Graham Brown Cancer Center,
University of Louisville, Louisville, KY, USA.
We reported that complement cascade (CC) becomes activated in bone
marrow (BM) during granulocyte colony-stimulating factor (G-CSF)
mobilization of hematopoietic stem/progenitor cells (HSPCs) and showed
that, although third CC component (C3)-deficient mice are easy
mobilizers, fifth CC component (C5)-deficient mice mobilize very poorly.
To explain this, we postulated that activation/cleavage of CC releases
C3a and C5a anaphylatoxins that differently regulate mobilization.
Accordingly, C3a, by enhancing responsiveness of HSPCs to decreasing
concentrations of stromal-derived growth factor-1 (SDF-1) in BM,
prevents mobilization and promotes their BM retention. Therefore, in
this study, we focused on the mobilization-enhancing role of C5a. We
found that C5a receptor (C5aR) is not expressed on the surface of HSPCs,
and that C5a-mediated promobilization effects are mediated by
stimulation of granulocytes. Overall, our data support the following
model. First C5aR(+) granulocytes are chemoattracted by plasma C5
cleavage fragments, being the first wave of cells leaving BM. This
facilitates a subsequent egress of HSPCs. In the next step, after
leaving BM, granulocytes undergo degranulation in response to plasma C5a
and secrete some cationic peptides (cathelicidin, beta-defensin) that,
as shown here for the first time, highly enhance the responsiveness of
HSPCs to plasma SDF-1 gradient. In conclusion, our data reveal the
underappreciated central role of innate immunity in mobilization, in
which C5 cleavage fragments through granulocytes orchestrate this
process.Leukemia advance online publication, 6 August 2009;
doi:10.1038/leu.2009.158.
PMID: 19657368
Ernie
asshole farrel and the rest of the snake oilers insist that MPB is
caused by dht. Ernie