MIP-1
is an acidic protein. The two variants, designatedMIP-1-alpha
andMIP-1-beta have a length of 69 amino acids (7.8 kDa).
At the protein level they show a homology of 60 percent.
Their cDNAs show a homology of 57 percent. The cDNA sequences
of MIP-alpha and MIP-beta demonstrate that they are the
murine homologs of human GRO-beta and GRO-gamma. MIP-1-alpha
is called also EP (endogenous pyrogen), SIS-alpha (small
inducible secreted; see: SIS family of cytokines ), L2G25B
, SCYA3 , and TY5 . MIP-1-alpha has been renamed CCL3,
recently. MIP-1-beta has been renamed CCL4 Both MIP proteins
belong to the family of chemotactic cytokines known as
Chemokines . MIP-1-alpha has been shown to bind to a receptor
called CKR-1 (chemokine receptor 1) It also binds to a
receptor designated D6. Chromosomal aberrations in region
17q11 are observed frequently in Recklinghausen neurofibromatosis.
Reciprocal translocations involving this regions are observed
also in 90-100 percent of acute promyelocytic leukemia.
At present it is not known whether there is an involvement
of these genes in these diseases. The two MIP proteins
are the major factors produced by macrophages following
their stimulation with bacterial endotoxins . Both proteins
are involved in the cell activation of human granulocytes
(neutrophils, eosinophils, and basophils) and appear to
be involved in acute neutrophilic Inflammation . Both forms
of MIP-1 stimulate the production of reactive oxygen species
in neutrophils and the release of lysosomal enzymes. They
also induce the synthesis of other pro-inflammatory cytokines
such as IL1 , IL6 and TNF in fibroblasts and macrophages
(see also: Inflammation ). MIP-1-alpha is a potent basophil
agonist, inducing a rapid change of cytosolic free calcium
(see also: Calcium ionophore ), the release of histamine
and sulfido-leukotrienes, and Chemotaxis . Murine MIP-1-alpha
is the primary stimulator of TNF secretion by macrophages,
whereas MIP-1-beta antagonizes the inductive effects of
MIP-1-alpha . In human monocytes the production of MIP-1-beta
can be induced by bacterial lipopolysaccharides and IL7.
MIP-1-beta is most effective at augmenting adhesion of
CD8 (+)T-cells (see also: CD antigens ) to the vascular
cell adhesion molecule VCAM-1 and it does so by being present
on the surface of endothelial cells complexed with endothelial
proteoglycans.
|
