chemokine Flashcards
chemokine function and classification
chemokine are primarily signpost for leukocytes to sites of inflammation and between immunological compartment (homeostasis conditions).
they determine the direction of chemotaxis with a gradient
structurally they differ by the position of NH2 terminal cysteine residues - they are 15 CXC chemokine and 25 CC chemokine
hey also can be differentiated based on their biological function: the one that are inducible and pro inflammatory scubas CCL2
and the one that are constitutive and homeostatic such as CCL19
GPCR signal
gene transcription through NFKB
cytoskeletal restructuring such as cdc42
firm addition
respiratory burst
cell survival with ERK
receptor internalisation
CXCL8
mobilise netruophlic granulocyte
induce neutrophil migration (mir slide bidi)
MMP9 release ( zymography)
FLIPR for intracellular calcium flux after CXCR1 and CXCR2 binding
it is the most potent in term of neutrophilic chemoattractant I humans
can sometimes also attract lymphocyte but need higher concentration
it is angiogenic and induce neovascularisation
in can be produced by almost any cells after a treatment with inflammatory mediators
their role in pathology is - enhancement of CXCR8 in serum is correlated with worse prognosis in cancer
AB for CXCR1 and 2 are in development to treat ischemia and re-perfusion injury
they are very important using extracellular bacterial infection
L-selectin
presents on leukocytes, highly expressed on naive T ell and low expression on effector and memory T cell
they bind to PNAd of endothelial cells
E-selectin
are endothelium activated by cytokine such as TNF alpha and IL1
they bind o surface protein of granulocyte, monoxide, effector T and memory T
P-selectin
storage of granules and surface of endothelial cells and platelets
hey bind to PSGL1 of granulocyte monocyte effector and memory T
Sialyl LewisX
It is known to play a vital role in cell-to-cell recognition processes
isolation and identification of postranslational modified chemokines
source are cell cultures with inflammatory mediators
they are the pureed using a screening ELISA assay
they are then identified through Edamn degradation and mass spec
the production for biological characterization is then carried through cleavage of recombinant chemokine with pure protease and chemical synthesis of truncated chemokine
the protease change the biological activity some CC and CXC chemokine ar substrate for this CD26 protease
CD26 and CCL5
dipeptidyl petidase
its effects on RANTES activity is various
truncated RANTES is an inhibitor go monocyte chemotaxis, it has a chemotactic activity that is reduced in monocyte and eosinophil but not altered on lymphocyte (CCR5)
CD26 and CCL11 (Eotaxin)
CCL11 s a chemoattractant of TH2 lymphocyte, basophils and eosinophils.
CCL11 is produced by epithelial cells through the STAT6 pathways and is involved in the protection against helminths infections
it is also a very important chemokine in allergic reaction such as in asthma.
After cleavage with CD26, CCL11 still binds to CCR3
however, truncated CCL111 does not induce migration of eosinophilic granulocyte
CD26 can therefore have an inactivation role such as here
or an activation role as seen with RANTES
