What is the difference between diapedesis and extravasation

Integrin structure, activation, and interactions. Cold Spring Harb. Herter, J. Integrin regulation during leukocyte recruitment. Luo, B. Structural basis of integrin regulation and signaling. Moser, M. The tail of integrins, talin, and kindlins. Science , — Abram, C. The ins and outs of leukocyte integrin signaling.

Rev, Immunol. Zarbock, A. Leukocyte ligands for endothelial selectins: specialized glycoconjugates that mediate rolling and signaling under flow. Blood , — Kuwano, Y. Rolling on E- or P-selectin induces the extended but not high-affinity conformation of LFA-1 in neutrophils.

Lefort, C. Distinct roles for talin-1 and kindlin-3 in LFA-1 extension and affinity regulation. This study shows that activation of the integrin LFA1 to the intermediate-affinity conformation, which supports slow leukocyte rolling, requires only the binding of talin, whereas activation to the high-affinity conformation requires binding of talin and kindlin 3.

Yago, T. Blocking neutrophil integrin activation prevents ischemia-reperfusion injury. Choi, E. Del-1, an endogenous leukocyte-endothelial adhesion inhibitor, limits inflammatory cell recruitment. Developmental endothelial locus-1 is a homeostatic factor in the central nervous system limiting neuroinflammation and demyelination.

Psychiatry 20 , — Kempf, T. GDF is an inhibitor of leukocyte integrin activation required for survival after myocardial infarction in mice.

Phillipson, M. Intraluminal crawling of neutrophils to emigration sites: a molecularly distinct process from adhesion in the recruitment cascade. Halai, K. ICAM-2 facilitates luminal interactions between neutrophils and endothelial cells in vivo. Cell Sci. Auffray, C.

Monitoring of blood vessels and tissues by a population of monocytes with patrolling behavior. Sumagin, R. LFA-1 and Mac-1 define characteristically different intralumenal crawling and emigration patterns for monocytes and neutrophils in situ.

Carlin, L. Nr4a1-dependent Ly6C low monocytes monitor endothelial cells and orchestrate their disposal. Cell , — Effector T cell interactions with meningeal vascular structures in nascent autoimmune CNS lesions.

Nature , 94—98 Barreiro, O. Carman, C. A transmigratory cup in leukocyte diapedesis both through individual vascular endothelial cells and between them. Transcellular diapedesis is initiated by invasive podosomes.

Immunity 26 , — RhoG regulates endothelial apical cup assembly downstream from ICAM1 engagement and is involved in leukocyte trans -endothelial migration.

Shaw, S. Yang, L. Endothelial cell cortactin coordinates intercellular adhesion molecule-1 clustering and actin cytoskeleton remodeling during polymorphonuclear leukocyte adhesion and transmigration. Endothelial cell cortactin phosphorylation by Src contributes to polymorphonuclear leukocyte transmigration in vitro.

Schnoor, M. Cortactin deficiency is associated with reduced neutrophil recruitment but increased vascular permeability in vivo.

Baluk, P. Endothelial gaps and adherent leukocytes in allergen-induced early- and late-phase plasma leakage in rat airways. He, P. Woodfin, A. The junctional adhesion molecule JAM-C regulates polarized transendothelial migration of neutrophils in vivo.

This paper visualizes for the first time leukocyte extravasation in vivo by 3D live imaging. It determines the numbers of paracellular and transcellular diapedesing neutrophils and demonstrates that the lack of JAMC leads to reverse transmigration of neutrophils.

Martin-Padura, I. Junctional adhesion molecule, a novel member of the immunoglobulin superfamily that distributes at intercellular junctions and modulates monocyte transmigration. Ostermann, G. Scott, D. N-glycosylation controls the function of the junctional adhesion molecule-A. Cell 26 , — Khandoga, A. Junctional adhesion molecule-A deficiency increases hepatic ischemia-reperfusion injury despite reduction of neutrophil transendothelial migration.

This study shows for the first time that two adhesion receptors function sequentially during neutrophil diapedesis in postcapillary venules. Corada, M. Junctional adhesion molecule-A-deficient polymorphonuclear cells show reduced diapedesis in peritonitis and heart ischemia-reperfusion injury. Natl Acad. USA , — Schmitt, M. Endothelial junctional adhesion molecule-a guides monocytes into flow-dependent predilection sites of atherosclerosis.

Circulation , 66—76 Zen, K. Cell 15 , — Aurrand-Lions, M. Junctional adhesion molecule-C regulates the early influx of leukocytes into tissues during inflammation. Colom, B. Leukotriene B4-neutrophil elastase axis drives neutrophil reverse transendothelial cell migration in vivo. Immunity 42 , — Nasdala, I. A transmembrane tight junction protein selectively expressed on endothelial cells and platelets. Conway, D. Cell Adh. Liao, F. Migration of monocytes across endothelium and passage through extracellular matrix involve separate molecular domains of PECAM Wakelin, M.

An anti-platelet-endothelial cell adhesion molecule-1 antibody inhibits leukocyte extravasation from mesenteric microvessels in vivo by blocking the passage through the basement membrane. Soluble domain 1 of platelet-endothelial cell adhesion molecule PECAM is sufficient to block transendothelial migration in vitro and in vivo. Thompson, R. Platelet endothelial cell adhesion molecule deficiency or blockade significantly reduces leukocyte emigration in a majority of mouse strains.

Bixel, G. Mouse CD99 participates in T cell recruitment into inflamed skin. Dufour, E. CD99 is essential for leukocyte diapedesis in vivo. Cell Commun. Bixel, M. A CDrelated antigen on endothelial cells mediates neutrophil but not lymphocyte extravasation in vivo. Seelige, R. Endothelial-specific gene ablation of CD99L2 impairs leukocyte extravasation in vivo.

Stefanidakis, M. Azcutia, V. Endothelial CD47 promotes vascular endothelial-cadherin tyrosine phosphorylation and participates in T cell recruitment at sites of inflammation in vivo. Sullivan, D. Watson, R. Endothelial CD99 signals through soluble adenylyl cyclase and PKA to regulate leukocyte transendothelial migration. Sorokin, L. The impact of the extracellular matrix on inflammation.

Schenkel, A. CD99 plays a major role in the migration of monocytes through endothelial junctions. Liao, F. Migration of monocytes across endothelium and passage through extracellular matrix involve separate molecular domains of CD Pober, J. Overlapping patterns of activation of human endothelial cells by interleukin 1, tumor necrosis factor and immune interferon. May, M. Nortamo, P.

The expression of human intercellular adhesion molecule-2 is refractory to inflammatory cytokines. Dustin, M. Gopalan, P. Preferential sites for stationary adhesion of neutrophils to cytokine-stimulated HUVEC under flow conditions. Wojciechowski, J. Preferential firm adhesion of leukocytes to a region near the endothelial junction during the inflammatory response in venules. Google Scholar. Issekutz, A. McLaughlin, F.

Cell Adhes. Wright, S. USA 85 , — Liu, Y. Human junction adhesion molecule regulates tight junction resealing in epithelia. Cell Science , — Ozaki, H. Cunningham, S. Facilitation by JAM3. Santoso, S. The junctional adhesion molecule 3 JAM-3 on human platelets is a counterreceptor for the leukocyte integrin Mac Berlin, C. Alpha 4 integrins mediate lymphocyte attachment and rolling under physiologic flow. Cell 80 , — Alon, R. Cell Biol. Berman, M. Abbassi, O.

E-selectin supports neutrophil rolling in vitro under conditions of flow. Luscinskas, F. Kitayama, J. Shear stress affects migration behavior of polymorphonuclear cells arrested on endothelium. Cuvelier, S. Shear-dependent eosinophil transmigration on interleukin 4-stimulated endothelial cells: A role for endothelium-associated eotaxin Allport, J.

Chronic inflammation also contributes to heart disease, Alzheimer's disease, diabetes, and cancer. Learning Objectives Describe the 4 processes that make up the inflammatory mechanism. Briefly describe the various beneficial effects of inflammation that are associated with plasma leakage and with diapedesis. Briefly describe the process of diapedesis, indicating the role of P-selectins, integrins, and adhesion molecules. Briefly describe the healing stage of inflammation. Briefly describe the problems that arise from chronic inflammation.

The Mechanism of Inflammation Essentially, four processes make up the inflammatory mechanism: a. Animation showing a capillary prior to vasodilation. Animation showing vasodilation. You Tube animation illustrating leukocyte rolling along the inner wall of a blood vessel. You Tube movie and animation of leukocyte extravasation diapedesis from ImmuneDocumentary. Early Inflammation and Diapedesis Most leukocyte diapedesis extravasation occurs in post-capillary venules because hemodynamic shear forces are lower in these venules.

During the very early stages of inflammation, stimuli such as injury or infection trigger the release of a variety of mediators of inflammation such as leukotrienes, prostaglandins, and histamine.

The binding of these mediators to their receptors on endothelial cells leads to vasodilation, contraction of endothelial cells, and increased blood vessel permeability.

In addition, the basement membrane surrounding the capillaries becoming rearranged so as to promote the migration of leukocytes and the movement of plasma macromolecules from the capillaries into the surrounding tissue.

Mast cells in the connective tissue as well as basophils, neutrophils and platelets leaving the blood from injured capillaries, release or stimulate the synthesis of vasodilators such as histamine, leukotrienes, kinins, and prostaglandins.

Certain products of the complement pathways C5a and C3a can bind to mast cells and trigger their release their vasoactive agents. In addition, tissue damage activates the coagulation cascade and production of inflammatory mediators like bradykinins. The binding of histamine to histamine receptors on endothelial cells triggers an upregulation of P-selectin molecules and platelet-activating factor or PAF on the endothelial cells that line the venules. The P-selectins then are able to reversibly bind to corresponding P-selectin glycoprotein ligands PSGL-1 on leukocytes.

This reversible binding enables the leukocyte to now roll along the inner wall of the venule. The binding of PAF to its corresponding receptor PAF-R on the leukocyte upregulates the surface expression of an integrin called leukocyte function-associated molecule-1 LFA-1 on the surface of the leukocyte. The leukocytes flatten out, squeeze between the constricted endothelial cells, and use enzymes to breakdown the matrix that forms the basement membrane surrounding the blood vessel.

Late Inflammation and Diapedesis 1 Usually within two to four hours of the early stages of inflammation, activated macrophages and vascular endothelial cells release inflammatory cytokines such as TNF and IL-1 when their toll-like receptors bind pathogen-associated molecular patterns - molecular components associated with microorganisms but not found as a part of eukaryotic cells.

For More Information: Cytokines from Unit 5. Animation summarizing late inflammation and diapedesis. Benefits of Inflammation As a result of this increased permeability: a. For More Information: Antibodies from Unit 6. For More Information: Leukocytes from Unit 5. Concept Map for Inflammation. Exercise: Think-Pair-Share Questions Briefly describe the mechanisms that enable to slow the flow of blood at an infection site and get phagocytes, complement proteins and antibodies to the infection site.

Why is it important to deliver plasma to an infection site? Why is it important for diapedesis to occur during inflammation? Summary Most of the body defense elements are located in the blood and inflammation is the means by which body defense cells and defense chemicals leave the blood and enter the tissue around the injured or infected site.

As part of the mechanism for inflammation, smooth muscles around larger blood vessels contract to slow the flow of blood through the capillary beds at the infected or injured site. As part of the mechanism for inflammation, the endothelial cells that make up the wall of the smaller blood vessels contract.

As part of the mechanism for inflammation, adhesion molecules are activated on the surface of the endothelial cells on the inner wall of the capillaries and corresponding molecules on the surface of leukocytes called integrins attach to these adhesion molecules allowing the leukocytes to flatten and squeeze through the space between the endothelial cells.