Macrophage Inflammatory Proteins (MIP) belong to the family of chemotactic

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 a ...

s known as

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

s. 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, 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 macrophages 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 i ...

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 am ...

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 m ...

or proinflammatory cytokines such as IL-1β. 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 (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 pr ...

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

s, T lymphocytes,

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 repres ...

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 i ...

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 ...

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. ...

s and basophils) 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 ...

(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 homolo ...

from

fibroblast A fibroblast is a type of biological cell that synthesizes the extracellular matrix and collagen, produces the structural framework ( stroma) for animal tissues, and plays a critical role in wound healing. Fibroblasts are the most common cells of ...

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 ...

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. 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 intercellu ...

and is responsible for chemotaxis of dendritic cells and macrophages into Peyer's patches 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 ...

and CXCR2. 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 ...

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 weakl ...

is produced by mucosa and skin by activated epithelial cells and attracts

Th17 cells T helper 17 cells (Th17) are a subset of pro-inflammatory T helper cells defined by their production of interleukin 17 (IL-17). They are related to T regulatory cells and the signals that cause Th17s to differentiate actually inhibit Treg different ...

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 ...

s and immature

s and has part in migration of these cells in secondary lymphoid organs. Mature dendritic cells down-regulate CCR6 and up-regulate

CCR7 C-C chemokine receptor type 7 is a protein that in humans is encoded by the ''CCR7'' gene. Two ligands have been identified for this receptor: the chemokines (C-C motif) ligand 19 (CCL19/ELC) and (C-C motif) ligand 21 (CCL21). CCR7 has also recen ...

, which is receptor for MIP-3β. MIP-3β (

CCL19 Chemokine (C-C motif) ligand 19 (CCL19) is a protein that in humans is encoded by the ''CCL19'' gene. This gene is one of several CC cytokine genes clustered on the p-arm of chromosome 9. Cytokines are a family of secreted proteins involved in im ...

) is produced by stromal cells in T-cell zones of secondary lymphoid organs 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 inc ...

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 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, c ...

References

External links