Biomedical Engineering Reference
In-Depth Information
(LFA-1, integrin α
L
β
2
, CD11a/CD18) and macrophage-1 antigen (Mac-1, integrin
α
M
β
2
, CD11b/CD18), and the β
1
family, including VLA-4 (integrin α
4
β
1,
CD49d/
CD29), have been shown to be crucial elements of the leukocyte recruitment
pathway in skin and other tissues.
Adhesion Molecules in Transmigration and Diapedesis
Transmigration across the endothelium and basement membrane and movement
within the tissue are the i nal steps in the process of leukocyte recruitment into
the skin. A detailed description of the variety of molecules involved in endothelial
transmigration is available in recent reviews (Ley
et al.
2007, Vestweber 2007).
Briel y, a complex interplay of endothelial junctional proteins and leukocyte
surface glycoproteins, including PECAM-1, junctional adhesion molecules, CD99,
LFA-1/ICAM-1 complexes, and VE-cadherin, supports and directs leukocyte
transmigration through and around endothelial cells and into the underlying
extravascular space. Adding to this complexity, transmigrating leukocytes express
surface proteases that are selective for basement membrane proteins, thereby
exposing new or hidden binding sites for adhesion molecules, and/or generating
protein fragments that can be chemotactic and recruit additional cells into the
involved tissue.
IMMUNE SURVEILLANCE IN SKIN
In this section, we discuss the ways in which selective leukocyte recruitment drives
immune surveillance and response in peripheral tissues.
Innate Immune Surveillance
Ef ective host defense against invading microorganisms requires detection of
foreign invaders. In higher vertebrates, the immune system has developed rapid
non-specii c (innate), and sustained specii c (adaptive) mechanisms to defend
the host against pathogen invasion. Central to our understanding of cutaneous
innate immune surveillance is the observation that cells resident in skin serve
as sentinels for danger signals, including pathogen invasion and physical injury.
We have reviewed these concepts in detail elsewhere and will discuss them only
briel y here (Kupper and Fuhlbrigge 2004, Clark and Kupper 2005). Keratinocytes
and Langerhans cells in the epidermis, as well as dermal dendritic cells, mast cells
and macrophages, express a variety of pattern recognition receptors (PRR) that
recognize conserved molecular patterns found on microbial pathogens and trigger
downstream activation cascades and release of antimicrobial peptides, chemotactic
proteins, and inl ammatory cytokines. An important subset of these PRR belong
to the toll-like receptor (TLR) family, which recognize pathogen-associated
