Chemokine (C-C motif) ligand 3 (CCL3) also known as macrophage inflammatory protein 1-alpha (MIP-1-alpha) is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
that in humans is encoded by the ''CCL3''
gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
.
Function
CCL3 is a
cytokine
Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in autocrin ...
belonging to the
CC chemokine family that is involved in the acute inflammatory state in the recruitment and activation of
polymorphonuclear leukocyte
Granulocytes are
cells in the innate immune system characterized by the presence of specific granules in their cytoplasm. Such granules distinguish them from the various agranulocytes. All myeloblastic granulocytes are polymorphonuclear. They hav ...
s
through binding to the receptors
CCR1
C-C chemokine receptor type 1 is a protein that in humans is encoded by the ''CCR1'' gene.
CCR1 has also recently been designated CD191 (cluster of differentiation 191).
Function
This gene encodes a member of the beta chemokine receptor fami ...
,
CCR4
C-C chemokine receptor type 4 is a protein that in humans is encoded by the ''CCR4'' gene. CCR4 has also recently been designated CD194 (cluster of differentiation 194).
The protein encoded by this gene belongs to the G protein-coupled receptor f ...
and
CCR5
C-C chemokine receptor type 5, also known as CCR5 or CD195, is a protein on the surface of white blood cells that is involved in the immune system as it acts as a receptor for chemokines.
In humans, the ''CCR5'' gene that encodes the CCR5 p ...
.
Sherry et al. (1988) demonstrated 2 protein components of MIP1, called by them alpha (CCL3, this protein) and beta (
CCL4
Chemokine (C-C motif) ligands 4 (also CCL4) previously known as macrophage inflammatory protein (MIP-1β), is a protein which in humans is encoded by the ''CCL4'' gene. ''CCL4'' belongs to a cluster of genes located on 17q11-q21 of the chromosom ...
).
CCL3 produces a monophasic fever of rapid onset whose magnitude is equal to or greater than that of fevers produced with either recombinant human
tumor necrosis factor
Tumor necrosis factor (TNF, cachexin, or cachectin; formerly known as tumor necrosis factor alpha or TNF-α) is an adipokine and a cytokine. TNF is a member of the TNF superfamily, which consists of various transmembrane proteins with a homolog ...
or recombinant human
interleukin-1
The Interleukin-1 family (IL-1 family) is a group of 11 cytokines that plays a central role in the regulation of immune and inflammatory responses to infections or sterile insults.
Discovery
Discovery of these cytokines began with studies on t ...
. However, in contrast to these two endogenous
pyrogens, the fever induced by MIP-1 is not inhibited by the
cyclooxygenase
Cyclooxygenase (COX), officially known as prostaglandin-endoperoxide synthase (PTGS), is an enzyme (specifically, a family of isozymes, ) that is responsible for formation of prostanoids, including thromboxane and prostaglandins such as prosta ...
inhibitor
ibuprofen
Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) that is used for treating pain, fever, and inflammation. This includes painful menstrual periods, migraines, and rheumatoid arthritis. It may also be used to close a patent ductus arte ...
and CCL3 may participate in the
febrile response
Fever, also referred to as pyrexia, is defined as having a temperature above the normal range due to an increase in the body's temperature set point. There is not a single agreed-upon upper limit for normal temperature with sources using val ...
that is not mediated through
prostaglandin
The prostaglandins (PG) are a group of physiologically active lipid compounds called eicosanoids having diverse hormone-like effects in animals. Prostaglandins have been found in almost every tissue in humans and other animals. They are derive ...
synthesis and clinically cannot be ablated by cyclooxygenase.
Interactions
CCL3 has been shown to
interact
Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex traits. The organizati ...
with
CCL4
Chemokine (C-C motif) ligands 4 (also CCL4) previously known as macrophage inflammatory protein (MIP-1β), is a protein which in humans is encoded by the ''CCL4'' gene. ''CCL4'' belongs to a cluster of genes located on 17q11-q21 of the chromosom ...
.
Attracts macrophages, monocytes and neutrophils.
See also
*
Macrophage inflammatory protein
Macrophage Inflammatory Proteins (MIP) belong to the family of chemotactic cytokines known as chemokines. In humans, there are two major forms, MIP-1α and MIP-1β that are now (according to the new nomenclature) officially named CCL3 and CCL4, ...
s
References
External links
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Further reading
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Cytokines
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