Topic 2 lecture note..

abnormalities in postsurgical leukocyte rolling in cremaster venules. Antibodies blocking
L-selectin function reduced rolling in CD34 deficient mice suggesting that CD34 lacks
major significance as a ligand for L-selectin.
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Chemoattractants
Extracellular matrix
In a lot of the connective tissues, the extracellular matrix molecules are secreted by cells
called fibroblasts. These molecules assemble into the extracellular matrix once they are
secreted. The extracellular matrix is made up of two classes of macromolecules. The first
class is called glycosaminoglycans, which are polysaccharide chains. Members of this
class are usually found to be covalently linked to protein in the form of proteoglycans.
The second class is made up by fibrous proteins. There are two functional types of
fibrous proteins: the ones that are mainly structural, like collagen and elastin for example,
and the ones that are mainly adhesive, like fibronectin and laminin for example. The
members of the glycosaminoglycans form a highly hydrated, gel-like substance, in which
the members of the fibrous proteins are embedded. Collagen fibers strengthen and help to
organize the matrix, while elastin fibres give it resiliance. The adhesive proteins help
cells to attach to the extracellular matrix. Fibronectin for example promotes the
attachment of fibroblasts and other cells to the matrix in connective tissues via the
extracellular parts of some members of the integrin family, while laminin promotes the
attachment of epithelial cells to the basal lamina, again via the extracellular domains of
some members of integrins.
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Multistep process of leukocyte extravasation
The stimulus for endothelial activation in vivo is probably local production of cytokines
and other inflammatory mediators released on tissue injury.
Capture
The process known as capture or tethering represents the first contact of a leukocyte with
the activated endothelium. Capture occurs after margination, which allows leukocytes to
move in a position close to the endothelium, away from the central blood stream. During
the inflammatory response, endothelial activation is required to initiate capture.
P-selectin on endothelial cells, is the primary adhesion molecule for capture and the
initiation of rolling. The main leukocyte ligand for P-selectin is PSGL-1. In addition,
many in vivo studies suggest that L-selectin exhibits an important role in capture as well.
Antibodies blocking L-selectin function inhibit rolling in many models in which rolling is
P-selectin dependent.
EFigure 10. Expression of ICAM-3 (CD50)
E-cadherin.10)