白细胞

While red blood cells are carried away at high velocity by a strong blood flow, leukocytes roll slowly on endothelial cells. P-selectins on endothelial cells interact with PSGL-1, a glycoprotein on leukocyte microvilli. Leukocytes, pushed by the blood flow, adhere and roll on endothelial cells, because existing interaction are broken, while new ones are formed. These interactions are possible because the extended extra cellular domains of both proteins emerge from the extra cellar matrix, which cover the surface of both cell types.

The outer leaflet of the lipid bilayers is enriched in sphingolipids and phosphatidylcholine. Sphingolipid-rich raft raise above the rest of the leaflet, recruit specific membrane proteins. Raft rigidity is caused by the tight packing of cholesterol molecules against the straight sphingolipids hydrocarbon chains. Outside the raft, kinks and unsaturated hydrocarbon chain, and lower cholestrol concentration, result in increased fluidity.

At sites of inflammation, secreted chemokine bound to heparin sulfate proteoglycan

on

endothelial

cells

are

presented

to

leukocyte

seven-transmembrane receptors. The binding stimulates leukocytes, and triggers an intercellular cascade of signalling reactions.

The inner leaflet of the bilayer has a very different composition than that of the outer leaflet. While some proteins traverse the membrane, others are either anchored to the inner leaflet by covalently attached fatty acid chains, or are recruited through non-covalent interaction with membrane proteins. The membrane-bond protein complexes are critical for the transmission of signals

across the plasma membrane.

Beneath the lipid bilayer, spectrin tetramers, arranged into a hexagonal network, are anchored by membrane protein. This network forms a membrane skeleton that contributes to membrane stability and membrane protein distribution. The cytoskeleton is comprised of networks of filamentous proteins that are responsible for the spatial organization of cytosolic components. Inside microvilli, actin filaments form tight parallel bundles which are stabalized by cross-linking proteins. While deeper in the cytosol, the actin network adopts a gel-like structure, stabalized by a variety of actin binding proteins. Filaments, capped at their minus end by a protein complex, grow away from the plasma membrane by the addition of actin monomers to their plus ends. The actin network is a very dynamic structure, with continuous directional polymerization and disassembly. Severing proteins induces kinks in the filaments, and leads to the formation of short fragments that rapidly depolymerize or give rise to new filaments. The cytoskeleton includes a network of microtubules created by the lateral association of protofilaments formed by the polymerization of tubulin dimers.

While the plus end of some microtubules extends toward the plasma membrane, proteins stabilize the curved conformation of the protofilaments from other microtubules, causing their rapid plus end depolymerization. Microtubules provide tracks along which membrane-bound vesicles travel to and from the plasma membrane. The directional movement of these cargo vesicles is due to a family of motor proteins linking vesicles and microtubules.

Membrane bound organells like mitochondria are loosely trapped by the cytoskeleton. Mitochondria change shape continuously, and their orientation is partly dictated by their interaction with microtubules. All the microtubule originates from the centrosome, a discrete fibrous structure containing two orthogonal centrioles and located near the cell nucleus. Pores of the nuclear envelope allow the import of particles containing mRNA and proteins into the cytosol. Here, free ribosomes translate the mRNA molecules into proteins. Some of these proteins are reside in the cytosol, others are associated with specialized cytosolic proteins and been imported into mitochondria or other organelles. The synthesis of cell-secreted and integral membrane proteins is initiated by free ribosomes, which than dock to protein translocator at the surface of the endoplasmic reticulum.

Nascent proteins pass through an aqueous pore in the translocator. Cell secreted proteins accumulated in the lumen of the endoplasmic reticulum, while integral membrane proteins become embedded in the endoplasmic reticulum membrane.

Proteins are transported from the endoplasmic reticulum to the Golgi apparatus by vesicles traveling along the microtubules.

Protein glycosylation, initiated in the endoplasmic reticulum, is completed inside the lumen of the Golgi apparatus. Fully glycosylated proteins are transported from the Golgi apparatus to the plasma membrane. While the vesicle fuses with the plasma membrane, proteins contained in the vesicle lumen are

secreted, and proteins embedded in the vesicle membrane diffuse in the cell membrane.

At sites of inflammation, chemokine secreted by endothelial cells binds to the extracellular domains of G-protein coupled membrane-receptors. This binding causes a conformational change in the cytosolic portion of the receptor, and the consequent activation of the subunit of the G-protein. The activation of the G-protein subunit triggers a cascade of protein activation, which in turn lead to the activation and clustering of integrin inside lipid rafts. A dramatic conformational change occurs in the extracellular domain of the activated integrins. This now allowed for their interaction with I-Cam proteins display at the surface of the endothelial cells. These strong interactions immobilized the rolling leukocyte at the site of inflammation. Additional signaling event cause a profound reorganization of the cytoskeleton, result in the spreading of one edge of the leukocyte.

The leading edge of the leukocyte inserts itself between the endothelial cells, and the leukocyte migrates through the blood vessel wall into the inflammed tissue.

Rolling, activation, adhesion, and trans-endothelial migration are the four steps of the process called leukocyte extravasation.