Biomedical Engineering Reference
In-Depth Information
P-selectin is constitutively synthesized by endothelial cells and platelets.
With endothelial activation by thrombin, histamine, phorbol ester, complement
proteins, cytoplasmic storage granules fuse with the cell membrane, externalizing
their contents. Such stimulation of endothelial cells leads to P-selectin-dependent
neutrophil adhesion lasting 1.5 to 4 hr. In contrast to ICAM-2 and P-selectin, there
is abundant evidence that E-selectin, ICAM-1 and VCAM-1 are transcriptionally
regulated by cytokines. Furthermore, there appears to be a dif erence between
endothelium in large vessels versus the microcirculation in the ability to express
these proteins. Again, all of these factors may contribute to the selective recruitment
of subsets of leukocytes during an inl ammatory or immune response.
ADHESION CASCADE
Elegant studies by interracial microscopy have identii ed a sequence of adhesive
interactions involved in leukocyte emigration from the bloodstream to
extravascular site of inl ammation. Because of lack of cilia, leukocytes cannot
swim to the vessel wall in response to extravascular chemotactic stimuli. Initial
contact with the vessel wall then is a random event, perhaps enhanced by local
alteration in l ow characterstics. Although 39% of leukocytes were observed to
roll along the endothelium of rat mesenteric venules, only 0.6% rolled along
the endothelium of arterioles. With sui cient tissue trauma or inl ammation, a
portion of the leukocytes are observed to l atten and spread on the endothelium
and then to stick i rmly. Occasionally, other leukocytes will stick to the leukocyte
adherent to the vessel wall, forming small aggregates of leukocytes attached to the
endothelium. Some of the adherent leukocytes crawl over the endothelial surface,
seeming to probe for an opening, and then diapedes or crawl between endothelial
cells; once in subendothelial tissue, the extravasated leukocytes continue to
migrate toward the inl ammatory site. In the i nal steps of the cascade, some of the
adherent leukocytes migrate between the inter-endothelial cell junctions, and then
through the subendothelial extracellular matrix to accumulate i nally at the site of
inl ammatory or immune reaction.
SELECTIVE RECRUITMENT
Experimental models of inl ammation have shown that the recruitment of
leukocyte subtypes follows a characteristic temporal sequence. h ere is ot en
selective recruitment of a leukocyte subtype in inl ammatory or immune
reaction. h e most striking example is the marked accumulation of eosinophils
at extravascular site of allergic rhinitis or alveolar spaces in asthma, although
eosinophils represent only a small percentage of circulating leukocytes. Also, in
synovial tissue in rheumatoid arthritis and in skin involved with inl ammatory
dermatoses there is a preponderance of memory T-cells that does not rel ect
