Glossary of terms

$\beta _2$ Integrins

The $\beta _2$ integrins involved in leucocyte rolling, adhesion and transmigration are a set of four heterodimers CD11a/CD18 (LFA-1), CD11b/CD18 (Mac-1), CD11c/CD18 (CR4,P150,P95) and CD11d/CD18. These integrins are expressed on the surface of leucocytes and interact with members of the immunoglobulin superfamily expressed on endothelial cells to perform tight adhesion and initiate transmigration. The immunoglobulin superfamily includes ICAM-1/2/3, PECAM-1 and VCAM-1.

A mutation in CD18 results in defective $\beta _2$ integrin function and is clinically manifest as LAD syndrome (Leukocyte Adhesion Deficiency).

CD

CD102

ICAM-2

CD106

VCAM-1

CD11a

Subunit of $\beta _2$ integrin LFA-1

CD11b

Subunit of $\beta _2$ integrin MAC-1

CD11c

Subunit of $\beta _2$ integrin P150

CD18

Subunit of $\beta _2$ integrins LFA-1, MAC-1, P150

CD31

PECAM-1

CD34

Ligand for L-Selectin

CD50

ICAM-3

CD54

ICAM-1

CD62E

E-Selectin

CD62L

L-Selectin

CD62P

P-Selectin

ICAM-1

Intra-cellular adhesion molecule one, ICAM-1 (CD54) member of the immunoglobulin superfamily which plays a role in endothelial leucocyte interaction. It weighs 75-115 Kd, is located on hematoponietic and non hematoponietic cells and binds to CD11a/CD18 (LFA-1) and CD11b/CD18 (Mac-1).

ICAM-2

Intracellular adhesion molecule-2 (CD102).

Member of the immunoglobulin superfamily which plays a role in endothelial leucocyte interaction. It weighs 55-65 Kd, is located on resting lymphocytes, monocytes and endothelial cells. It binds to CD11a/CD18 (LFA-1).

ICAM-3

Intracellular adhesion molecule-3 (CD50).

Member of the immunoglobulin superfamily which plays a role in endothelial leucocyte interaction It weighs 130 Kd, is located on thymocytes and binds to CD11a/CD18 (LFA-1) on leucocytes.

Immunogloblin superfamily molecules

These molecules are expressed on the surface of endothelial cells. The five members of the immunoglobulin superfamily that are involved in leucocyte rolling$\rightarrow$transmigration are ICAM-1/2/3, PECAM-1 and VCAM-1. The interact with $\beta _2$ integrins that are expressed on the surface of leucocytes. The $\beta _2$ integrins that they interact with are CD11a/CD18, CD11b/CD18, CD11c/CD18 and CD11d/CD18. The predominant $\beta _2$ integrin, CD11a/CD18 is also termed LFA-1. CD11b/CD18 is also termed MAC-1 and CD11c/CD18 is also termed P150.

LAD

Leukocyte adhesion deficiency, a genetic disorder due to mutation in CD18 the common $\beta$ subunit in $\beta _2$ integrins.

Patients with LAD, are susceptible to recurrent bacterial infections due to the inability to effectively recruit granulocytes.

LFA-1

Lymphocyte function associated antigen 1, aka. CD11a/CD18 a $\beta _2$ integrin expressed on leucocytes

Mac-1

aka. CD11b/CD18 a $\beta _2$ integrin expressed on granulocytes and monocytes which interacts with immunoglobulin superfamily molecule expressed on endothelial cells. Mac-1 is stored in specific intracellular granules. On expression of the surface of the cell Mac-1 is quiescent, and non sticky. Activated Mac-1 makes the leukocyte sticky and is felt to play a role in the recruitment of neutrophils to an inflammed site.

NADPH Oxidase

Enzyme responsible for the generation of oxygen free radicals in neutrophils.

$$O_2 \stackrel{\rm NADPH Oxidase}{\longrightarrow} O^.$$

Production of the harmful free radicals is limited by the supply of oxygen. This is in contrast to the situation in parenchymal ane endothelial cells where production of these reactive species is catalysed by xanthine oxidase and depends on the availability of the hypoxanthine substrate.

PAF

Platlet activated factor.

Inflammatory mediator formed from a membrane phospholipid by a variety of cells including, platlets, endothelial cells and leucocytes.

Induces shedding of L-selectin from leucocytes that have become adherent. Binds to a cell surface receptor to induce expression of Mac-1 (CD11b/CD18, $\beta _2$ integrin) which is stored in granules in granulocytes and macrophages. Expression of Mac-1 increased leucocyte adhesion and transmigration. Transmigration will increase vascular permeability inducing oedema.

Stimulates formation of oxygen free radicals and release of myeloperoxidase and lactoferrin.

Hypoxia induces endothelial cells to release PAF and increase expression of ICAM-1.

PECAM-1

Platlet-endothelial cell adhesion molecule-1 (CD31), member of the immunoglobulin superfamily which plays a role in endothelial leucocyte interaction

It is locate on the endothelium, leucocytes and platlets.

PG-H2

Prostaglandin H2

Product of arachadinoic acid metabolism via the cyclo-oxygenase pathway. Prostaglandin H2 is a potent vaso constrictor, that is normally produced by endothelial cells.

PG-I2

Prostaglandin I2

Product of arachadinoic acid metabolism via the cyclo-oxygenase pathway. Prostaglandin I2 is also know as prostacyclin. It is a potent vaso dilator, that is normally produced by endothelial cells.

Selectins

E-Selectin

Also known as CD62E, ELAM-1.

Molecular weight is 140 Kd. Located in the endothelium, the main ligand is the carbohydrate derivitive sialyated Lewis. It is responsible for sialated Lewis mediated leucocyte rolling.

L-Selectin

Leucocyte selectin, also known as CD62L, LAM-1, LECAM-1.

Molecular weight is 150 Kd. Located in B, T, NK cells and Monocytes. The main ligand is the carbohydrate derivitive sialyated Lewis. It binds to CD34 and is responsible for glycam mediated leucocyte rolling.

P-Selectin

Platlet selectin, also known as CD62P, PADGEM.

Glycoprotein with molecular weight of 140 Kd. It is located in platlets in $\alpha$ granules and in the Weibel-Palade body in endothelial cells. The main ligand is the carbohydrate derivitive sialyated Lewis. It is responsible for monocyte and leucocyte rolling.

VCAM-1

Vascular cell adhesion molecule-1 (CD106) , member of the immunoglobulin superfamily which plays a role in endothelial leucocyte interaction. It weighs 100-110 Kd and is located on endothelial cells. Its main ligand on the leucocyte is VLA-4, a $\beta_1$ integrin ( $\alpha_4\beta_1$). Expression of VCAM-1 increases adhesion of lymphocytes, monocytes, eosinophils and basophils. Some cancer cells particularly melanoma appear to use VCAM-1 to bind to the endothelium.

VLA-4

Very late antigen four. An ( $\alpha_4\beta_1$) integrin expressed on the surface of leucocytes. It is a member of the $\beta_1$ subfamily of integrins. It binds to VCAM-1 on endothelial cells.

Weibel-Palade body

The Weibel-Palade body is visible on electron microscopy of endothelial cells. It is the location of storage of P-Selectin. P-Selectin is also stored in the $\alpha$ granules of platlets.

Xanthine Oxidase

Enzyme responsible for the generation of oxygen free radicals in parenchymal and endothelial cells.

$$Hypoxanthine \stackrel{\rm Xanthine Oxidase}{\longrightarrow} O^.$$

Production of the harmful free radicals is limited by the supply of hypoxanthine, when the substrate is exhausted, no more free radicals are produced. This is in contrast to the situation in neutrophils where production of these reactive species is catalysed by NADPH Oxidase and depends on the availability of oxygen. The enzyme may be inhibited by allopurinol.