Macrophage Inflammatory Proteins (MIP) belong to the family of

chemotactic Chemotaxis (from '' chemo-'' + ''taxis'') is the movement of an organism or entity in response to a chemical stimulus. Somatic cells, bacteria, and other single-cell or multicellular organisms direct their movements according to certain chemical ...

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 ...

s known as

chemokine Chemokines (), or chemotactic cytokines, are a family of small cytokines or signaling proteins secreted by cells that induce directional movement of leukocytes, as well as other cell types, including endothelial and epithelial cells. In additio ...

s. In humans, there are two major forms, MIP-1α and MIP-1β that are now (according to the new nomenclature) officially named

CCL3 Chemokine (C-C motif) ligand 3 (CCL3) also known as macrophage inflammatory protein 1-alpha (MIP-1-alpha) is a protein that in humans is encoded by the ''CCL3'' gene. Function CCL3 is a cytokine belonging to the CC chemokine family that is i ...

and

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 ...

, respectively. However, other names can sometimes be encountered, especially in older literature, as LD78α, AT 464.1 and GOS19-1 for human CCL3 and AT 744, Act-2, LAG-1, HC21 and G-26 for human CCL4. Other macrophage inflammatory proteins include MIP-2, MIP-3 and MIP-5.

MIP-1

MIP-1α and MIP-1β are major factors produced by

macrophage Macrophages (abbreviated as M φ, MΦ or MP) ( el, large eaters, from Greek ''μακρός'' (') = large, ''φαγεῖν'' (') = to eat) are a type of white blood cell of the immune system that engulfs and digests pathogens, such as cancer cel ...

s and

monocyte Monocytes are a type of leukocyte or white blood cell. They are the largest type of leukocyte in blood and can differentiate into macrophages and conventional dendritic cells. As a part of the vertebrate innate immune system monocytes also inf ...

s after they are stimulated with

bacteria Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were among ...

endotoxin Lipopolysaccharides (LPS) are large molecules consisting of a lipid and a polysaccharide that are bacterial toxins. They are composed of an O-antigen, an outer core, and an inner core all joined by a covalent bond, and are found in the outer ...

or proinflammatory cytokines such as

IL-1β Interleukin-1 beta (IL-1β) also known as leukocytic pyrogen, leukocytic endogenous mediator, mononuclear cell factor, lymphocyte activating factor and other names, is a cytokine protein that in humans is encoded by the ''IL1B'' gene."Catabolin" ...

. But it appears that they can be expressed by all hematopoietic cells and some tissue cells such as fibroblasts, epithelial cells, vascular smooth muscle cells or platelets upon activation. They are crucial for immune responses towards infection and inflammation. CCL3 and CCL4 can bind to extracellular proteoglycans, which is not necessary for their function but it can enhance their bioactivity. The biological effect is carried out through ligation of chemokine 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 ...

(ligand CCL3) 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 pro ...

(ligands CCL3 and CCL4) and the signal is then transferred into the cell, thus these cytokines affect any cell that has these receptors. The main effect is inflammatory and mainly consists of

chemotaxis Chemotaxis (from '' chemo-'' + ''taxis'') is the movement of an organism or entity in response to a chemical stimulus. Somatic cells, bacteria, and other single-cell or multicellular organisms direct their movements according to certain chemica ...

and transendothelial migration but cells can be activated to release of some bioactive molecules also. These chemokines affect

T lymphocytes A T cell is a type of lymphocyte. T cells are one of the important white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell rec ...

dendritic cell Dendritic cells (DCs) are antigen-presenting cells (also known as ''accessory cells'') of the mammalian immune system. Their main function is to process antigen material and present it on the cell surface to the T cells of the immune system. ...

NK cells Natural killer cells, also known as NK cells or large granular lymphocytes (LGL), are a type of cytotoxic lymphocyte critical to the innate immune system that belong to the rapidly expanding family of known innate lymphoid cells (ILC) and represen ...

and

platelet Platelets, also called thrombocytes (from Greek θρόμβος, "clot" and κύτος, "cell"), are a component of blood whose function (along with the coagulation factors) is to react to bleeding from blood vessel injury by clumping, thereby ini ...

s. They, too, activate human

granulocyte 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 ha ...

s (

neutrophil Neutrophils (also known as neutrocytes or heterophils) are the most abundant type of granulocytes and make up 40% to 70% of all white blood cells in humans. They form an essential part of the innate immune system, with their functions varying in ...

eosinophil Eosinophils, sometimes called eosinophiles or, less commonly, acidophils, are a variety of white blood cells (WBCs) and one of the immune system components responsible for combating multicellular parasites and certain infections in vertebrates. A ...

s and

basophil Basophils are a type of white blood cell. Basophils are the least common type of granulocyte, representing about 0.5% to 1% of circulating white blood cells. However, they are the largest type of granulocyte. They are responsible for inflammator ...

s) which can lead to acute neutrophilic inflammation. They also induce the synthesis and release of other pro-inflammatory cytokines such as

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 ...

(IL-1), IL-6 and

TNF-α 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 ...

from

fibroblast A fibroblast is a type of cell (biology), biological cell that synthesizes the extracellular matrix and collagen, produces the structural framework (Stroma (tissue), stroma) for animal Tissue (biology), tissues, and plays a critical role in wound ...

s and macrophages. The genes for CCL3 and CCL4 are both located on human

chromosome 17 Chromosome 17 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 17 spans more than 83 million base pairs (the building material of DNA) and represents between 2.5 and 3% of the total D ...

and on murine chromosome 11. They are produced by many cells, particularly macrophages, dendritic cells, and lymphocytes. MIP-1 are best known for their chemotactic and proinflammatory effects but can also promote homeostasis. Biophysical analyses and mathematical modelling has shown that MIP-1 reversibly forms a polydisperse distribution of rod-shaped polymers in solution. Polymerization buries receptor-binding sites of MIP-1, thus depolymerization mutations enhance MIP-1 to arrest monocytes onto activated human endothelium. MIP-1γ is another macrophage inflammatory protein and according to the new nomenclature is named

CCL9 Chemokine (C-C motif) ligand 9 (CCL9) is a small cytokine belonging to the CC chemokine family. It is also called ''macrophage inflammatory protein-1 gamma'' (MIP-1γ), ''macrophage inflammatory protein-related protein-2'' (MRP-2) and CCF18, that ...

. It is produced mainly by follicle-associated

epithelial cells Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellula ...

and is responsible for chemotaxis of dendritic cells and macrophages into

Peyer's patch Peyer's patches (or aggregated lymphoid nodules) are organized lymphoid follicles, named after the 17th-century Swiss anatomist Johann Conrad Peyer. * Reprinted as: * Peyer referred to Peyer's patches as ''plexus'' or ''agmina glandularum'' (c ...

es in gut through binding of CCR1. MIP-1δ or MIP-5 (CCL15) binds also CCR1 and CCR3.

MIP-2

MIP-2 belongs to the CXC chemokine family, is named CXCL2 and acts through binding of

CXCR1 Interleukin 8 receptor, alpha is a chemokine receptor. This name and the corresponding gene symbol IL8RA have been replaced by the HGNC approved name C-X-C motif chemokine receptor 1 and the approved symbol CXCR1. It has also been designated as CD ...

and

CXCR2 Interleukin 8 receptor, beta is a chemokine receptor. ''IL8RB'' is also known as ''CXCR2'', and CXCR2 is now the IUPHAR Committee on Receptor Nomenclature and Drug classification-recommended name. Function The protein encoded by this gene is ...

. It is produced mainly by macrophages, monocytes and epithelial cells and is responsible for chemotaxis to the source of inflammation and activation of neutrophils.

MIP-3

There are two chemokines in the MIP-3 group. MIP-3α (CCL20) and MIP-3β (CCL19). MIP-3α is binding to receptor

CCR6 Chemokine receptor 6 also known as CCR6 is a CC chemokine receptor protein which in humans is encoded by the ''CCR6'' gene. CCR6 has also recently been designated CD196 (cluster of differentiation 196). The gene is located on the long arm of Chro ...

CCL20 Chemokine (C-C motif) ligand 20 (CCL20) or liver activation regulated chemokine (LARC) or Macrophage Inflammatory Protein-3 (MIP3A) is a small cytokine belonging to the CC chemokine family. It is strongly chemotactic for lymphocytes and weakly at ...

is produced by mucosa and skin by activated epithelial cells and attracts Th17 cells to the site of inflammation. It is also produced by Th17 cells themselves. It further attracts activated

B cell B cells, also known as B lymphocytes, are a type of white blood cell of the lymphocyte subtype. They function in the humoral immunity component of the adaptive immune system. B cells produce antibody molecules which may be either secreted or ...

s, memory

T cell A T cell is a type of lymphocyte. T cells are one of the important white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell r ...

s and immature

s and has part in migration of these cells in

secondary lymphoid organs The lymphatic system, or lymphoid system, is an organ system in vertebrates that is part of the immune system, and complementary to the circulatory system. It consists of a large network of lymphatic vessels, lymph nodes, lymphatic or lymphoid o ...

. Mature dendritic cells down-regulate CCR6 and up-regulate CCR7, which is receptor for MIP-3β. MIP-3β ( CCL19) is produced by stromal cells in T-cell zones of

and binds to CCR7 receptor through which attracts mature dendritic cells to

lymph node A lymph node, or lymph gland, is a kidney-shaped organ of the lymphatic system and the adaptive immune system. A large number of lymph nodes are linked throughout the body by the lymphatic vessels. They are major sites of lymphocytes that inclu ...

s. It is also produced by dendritic cells and attracts also naive T lymphocytes and B lymphocytes to homing into the lymph node, where

antigen In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response. ...

s can be presented to them by dendritic cells.

MIP-5

MIP-5 (sometimes called MIP-1δ) or

CCL15 Chemokine (C-C motif) ligand 15 (CCL15) is a small cytokine belonging to the CC chemokine family that is also known as leukotactin-1, MIP5 and HCC-2. CCL15 is expressed in liver, small intestine, colon, and in certain leukocytes and macrophages ...

binds to receptors CCR1 and CCR3. It has chemotactic properties for monocytes and eosinophils and is expressed by macrophages, basophils and some tissue cells. It is proposed to have a role in pathology of

asthma Asthma is a long-term inflammatory disease of the airways of the lungs. It is characterized by variable and recurring symptoms, reversible airflow obstruction, and easily triggered bronchospasms. Symptoms include episodes of wheezing, cou ...

References

External links