Weibel–Palade bodies are the
storage granules of
endothelial cell
The endothelium (: endothelia) is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and th ...
s, the cells that form the inner lining of the
blood vessel
Blood vessels are the tubular structures of a circulatory system that transport blood throughout many Animal, animals’ bodies. Blood vessels transport blood cells, nutrients, and oxygen to most of the Tissue (biology), tissues of a Body (bi ...
s and
heart
The heart is a muscular Organ (biology), organ found in humans and other animals. This organ pumps blood through the blood vessels. The heart and blood vessels together make the circulatory system. The pumped blood carries oxygen and nutrie ...
.
They manufacture, store and release two principal molecules,
von Willebrand factor
Von Willebrand factor (VWF) () is a blood glycoprotein that promotes primary hemostasis, specifically, platelet adhesion. It is deficient and/or defective in von Willebrand disease and is involved in many other diseases, including thrombotic thro ...
and
P-selectin
P-selectin is a type-1 transmembrane protein that in humans is encoded by the SELP gene.
P-selectin functions as a cell adhesion molecule (CAM) on the surfaces of activated endothelial cells, which line the inner surface of blood vessels, and a ...
, and thus play a dual role in
hemostasis
In biology, hemostasis or haemostasis is a process to prevent and stop bleeding, meaning to keep blood within a damaged blood vessel (the opposite of hemostasis is hemorrhage). It is the first stage of wound healing. Hemostasis involves three ...
and
inflammation
Inflammation (from ) is part of the biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. The five cardinal signs are heat, pain, redness, swelling, and loss of function (Latin ''calor'', '' ...
.
Etymology
Weibel–Palade bodies were initially described by the
Swiss
Swiss most commonly refers to:
* the adjectival form of Switzerland
* Swiss people
Swiss may also refer to: Places
* Swiss, Missouri
* Swiss, North Carolina
* Swiss, West Virginia
* Swiss, Wisconsin
Other uses
* Swiss Café, an old café located ...
anatomist
Anatomy () is the branch of morphology concerned with the study of the internal structure of organisms and their parts. Anatomy is a branch of natural science that deals with the structural organization of living things. It is an old scien ...
Ewald R. Weibel and the
Romanian physiologist
Physiology (; ) is the scientific study of functions and mechanisms in a living system. As a subdiscipline of biology, physiology focuses on how organisms, organ systems, individual organs, cells, and biomolecules carry out chemical and ...
George Emil Palade in 1964. Palade won
Nobel Prize in Physiology and Medicine
The Nobel Prize in Physiology or Medicine () is awarded yearly by the Nobel Assembly at the Karolinska Institute, Nobel Assembly at the Karolinska Institute for outstanding discoveries in physiology or medicine. The Nobel Prize is not a single ...
in 1974 for his work on the function of organelles in
cells.
Constituents
There are two major components stored within Weibel–Palade bodies. One is
von Willebrand factor
Von Willebrand factor (VWF) () is a blood glycoprotein that promotes primary hemostasis, specifically, platelet adhesion. It is deficient and/or defective in von Willebrand disease and is involved in many other diseases, including thrombotic thro ...
(vWF), a multimeric
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
that plays a major role in
blood
Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells.
Blood is com ...
coagulation
Coagulation, also known as clotting, is the process by which blood changes from a liquid to a gel, forming a thrombus, blood clot. It results in hemostasis, the cessation of blood loss from a damaged vessel, followed by repair. The process of co ...
. Storage of long polymers of vWF gives this specialized lysosomal structure an oblong shape and striated appearance on electron microscope. The other is
P-selectin
P-selectin is a type-1 transmembrane protein that in humans is encoded by the SELP gene.
P-selectin functions as a cell adhesion molecule (CAM) on the surfaces of activated endothelial cells, which line the inner surface of blood vessels, and a ...
, which plays a central role in the ability of
inflamed endothelial cells to recruit passing
leukocytes
White blood cells (scientific name leukocytes), also called immune cells or immunocytes, are cells of the immune system that are involved in protecting the body against both infectious disease and foreign entities. White blood cells are genera ...
(white blood cells), allowing them to exit the blood vessel (
extravasate) and enter the surrounding tissue, where they can migrate to the site of
infection
An infection is the invasion of tissue (biology), tissues by pathogens, their multiplication, and the reaction of host (biology), host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmis ...
or injury.
Additional Weibel–Palade body components are the chemokines
interleukin-8 and
eotaxin-3,
endothelin-1
Endothelin 1 (ET-1), also known as preproendothelin-1 (PPET1), is a potent vasoconstrictor peptide produced by vascular endothelial cells, as well as by cells in the heart (affecting contractility) and kidney (affecting sodium handling). The prote ...
,
angiopoietin-2,
osteoprotegerin
Osteoprotegerin (OPG), also known as osteoclastogenesis inhibitory factor (OCIF) or tumour necrosis factor receptor superfamily member 11B (TNFRSF11B), is a cytokine receptor of the tumour necrosis factor (TNF) receptor superfamily encoded by th ...
, the P-selectin cofactor
CD63/lamp3,
and
α-1,3-fucosyltransferase VI.
Production
Multimeric vWF is assembled head-to-head in the
Golgi apparatus
The Golgi apparatus (), also known as the Golgi complex, Golgi body, or simply the Golgi, is an organelle found in most eukaryotic Cell (biology), cells. Part of the endomembrane system in the cytoplasm, it protein targeting, packages proteins ...
from tail-to-tail vWF dimers. vWF multimers condense and twist into long, helical, mostly parallel tubules separated by a less dense matrix of
protein domain
In molecular biology, a protein domain is a region of a protein's Peptide, polypeptide chain that is self-stabilizing and that Protein folding, folds independently from the rest. Each domain forms a compact folded Protein tertiary structure, thre ...
s protruding from the tubules.
The Golgi then buds off
clathrin
Clathrin is a protein that plays a role in the formation of coated vesicles. Clathrin was first isolated by Barbara Pearse in 1976. It forms a triskelion shape composed of three clathrin heavy chains and three light chains. When the triskel ...
-coated vesicles which consist almost exclusively of vWF.
Immature Weibel–Palade bodies remain near the nucleus, where they acquire more membrane proteins and then disperse throughout the cytoplasm, carried along
microtubules
Microtubules are polymers of tubulin that form part of the cytoskeleton and provide structure and shape to eukaryotic cells. Microtubules can be as long as 50 micrometres, as wide as 23 to 27 nm and have an inner diameter between 11 an ...
by
kinesins.
[ Clathrin-coated vesicles bud from immature Weibel–Palade bodies, reducing their volumes, condensing their contents, and removing select membrane proteins. Maturing Weibel–Palade bodies may also fuse with each other.][
The only parallel organelle in physiology is the alpha''-''granule of ]platelet
Platelets or thrombocytes () are a part of blood whose function (along with the coagulation#Coagulation factors, coagulation factors) is to react to bleeding from blood vessel injury by clumping to form a thrombus, blood clot. Platelets have no ...
s, which also contains vWF. Weibel–Palade bodies are the main source of vWF, while α-granules probably play a minor role.
Secretion
Weibel-Palade bodies undergo a complex maturation process following their dissociation from the trans-Golgi network (TGN) which involves recruitment of a large number of membrane proteins. These include Rab GTPases such as Rab27A, Rab3B and Rab3D, Rab effectors and SNARE
SNARE proteins – "Soluble NSF attachment protein, SNAP REceptors" – are a large protein family consisting of at least 24 members in yeasts and more than 60 members in mammalian and plant cells.
The primary role of SNARE proteins is to m ...
proteins, which together form the exocytotic machinery of Weibel-Palade bodies.
The small subset of Weibel–Palade bodies tethered at the cell periphery to the actin cortex
Cortex or cortical may refer to:
Biology
* Cortex (anatomy), the outermost layer of an organ
** Cerebral cortex, the outer layer of the vertebrate cerebrum, part of which is the ''forebrain''
*** Motor cortex, the regions of the cerebral cortex i ...
serve as a readily releasable pool that's replenished by a larger pool of microtubule-associated bodies in the cell interior.
The contents of Weibel–Palade bodies are secreted by one of three mechanisms. Some undergo exocytosis
Exocytosis is a term for the active transport process that transports large molecules from cell to the extracellular area. Hormones, proteins and neurotransmitters are examples of large molecules that can be transported out of the cell. Exocytosis ...
individually in a rapid, sub-second fusion event, while others fuse transiently to the plasma membrane in a "lingering kiss" that opens a pore large enough for only their smaller cargo (e.g. IL-8, CD63) to diffuse out. In some cases this is accompanied by the formation of an actomyosin ring complex around the fusing Weibel-Palade body. Weibel–Palade bodies may also coalesce into larger vesicles called secretory pods, for multigranular exocytosis. Secretory pod formation is mediated by interposition of tiny nanovesicles between bodies. As Weibel–Palade bodies fuse together into secretory pods, their vWF cargo loses its tubular form for spaghetti-like strings that are then exocytosed through a fusion pore. Whether cargo besides vWF is exocytosed from secretory pods or selectively retained is uncertain. Different modes of cargo release from Weibel–Palade bodies may be a mechanism for differential release of subsets of molecules in different physiological conditions.
During secretion, the vWF molecules fuse together into the final concatamer "strings".
Clinical significance
The importance of Weibel–Palade bodies are highlighted by some human disease mutations. Mutations within vWF are the usual cause of the most common inherited bleeding disorder, von Willebrand disease
Von Willebrand disease (VWD) is the most common heredity, hereditary coagulopathy, blood-clotting disorder in humans. An acquired form can sometimes result from other medical conditions. It arises from a deficiency in the quality or quantity of ...
. VWD has an estimated prevalence in some human populations of up to 1%, and is most often characterized by prolonged and variable mucocutaneous bleeding. Type III von Willebrand Disease is a severe bleeding disorder, like severe hemophilia
Haemophilia (British English), or hemophilia (American English) (), is a mostly inherited genetic disorder that impairs the body's ability to make blood clots, a process needed to stop bleeding. This results in people bleeding for a long ...
type A or B. VWF acts in primary hemostasis
In biology, hemostasis or haemostasis is a process to prevent and stop bleeding, meaning to keep blood within a damaged blood vessel (the opposite of hemostasis is hemorrhage). It is the first stage of wound healing. Hemostasis involves three ...
to recruit platelets
Platelets or thrombocytes () are a part of blood whose function (along with the coagulation factors) is to react to bleeding from blood vessel injury by clumping to form a blood clot. Platelets have no cell nucleus; they are fragments of cyto ...
at a site of injury, and is also important in secondary hemostasis
In biology, hemostasis or haemostasis is a process to prevent and stop bleeding, meaning to keep blood within a damaged blood vessel (the opposite of hemostasis is hemorrhage). It is the first stage of wound healing. Hemostasis involves three ...
, acting as a chaperone for coagulation
Coagulation, also known as clotting, is the process by which blood changes from a liquid to a gel, forming a thrombus, blood clot. It results in hemostasis, the cessation of blood loss from a damaged vessel, followed by repair. The process of co ...
factor VIII (FVIII).
See also
* Endothelial activation
References
External links
*
{{DEFAULTSORT:Weibel-Palade body
Organelles