Topic 2 lecture note..

CLA binding E-selectin, LFA-1 to ICAM-1, VLA-4 to VCAM-1, which are stimulated
by endothelial-displayed TARC binding to CCR4 on leukocytes. Subsequent localization
within tissues may then be controlled by local production of other chemokines such as
MDC binding to CCR4, and CTACK binding to CCR10, and by VLA-1 and VLA-2.
Humans suffering from leukocyte adhesion deficiency syndrome-1 (LAD-1), due loss of
2 subunit, have frequent skin infections. The skin is devoid of neutrophils, and there are
reduced numbers of other leukocytes. CCR4 is highly expressed on CLA + memory T
cells. Its ligand TARC is present in venules of inflamed skin. TARC is expressed by
endothelial cells and stimulates T cell adhesion to ICAM-1. CTACK preferentially
activates homing to the skin of memory CLA + T cells. It is produced by keratinocytes
within the skin, and activates cells via CCR10. CCR4 and CCR10 may have overlapping
roles in cutaneous lymphocyte recruitment. CTACK may be transcytosed, and presented
on endothelium to support triggering of adhesion of skin-homing lymphocytes.
Eosinophils: Eosinophil migration into the skin during allergic cutaneous inflammation
involves P-selectin binding to PSGL-1, LFA-1 binding to ICAM-1, and VLA-4 binding
to VCAM-1, probably stimulated by eotaxin and eotaxin-3 binding to CCR3. Subsequent
localization may be mediated by CCR3-active chemokines, and by VLA-4, and VLA-6.
Human eosinophils express high levels of PSGL-1 and L-selectin. CCR3-active
chemokines such as RANTES, eotaxin, eotaxin-2, and MCP-4 are implicated in
eosinophil accumulation in skin. Intradermal injection of RANTES, or eotaxin-3 causes
selective and rapid accumulation of eosinophils.