RECRUITMENT OF LYMPHOCYTES DURING CUTANEOUS DELAYED-HYPERSENSITIVITY IN NONHUMAN-PRIMATES IS DEPENDENT ON E-SELECTIN AND VASCULAR CELL-ADHESION MOLECULE-1
A. Silber et al., RECRUITMENT OF LYMPHOCYTES DURING CUTANEOUS DELAYED-HYPERSENSITIVITY IN NONHUMAN-PRIMATES IS DEPENDENT ON E-SELECTIN AND VASCULAR CELL-ADHESION MOLECULE-1, The Journal of clinical investigation, 93(4), 1994, pp. 1554-1563
Previous investigations of cutaneous delayed hypersensitivity (DHR) in
humans and animals have demonstrated that lymphocyte recruitment from
blood is temporally and spatially associated with the de novo, asynch
ronous expression of both vascular cell adhesion molecule 1 (VCAM-1) a
nd E-selectin on dermal endothelium. In this study, DHR was induced in
rhesus monkeys sensitized against tuberculin in order to investigate
the contribution of E-selectin and VCAM-1 in lymphocyte recruitment to
skin. Intravenous infusions of neutralizing doses of F(ab')(2) fragme
nts of murine antibodies to either E-selectin or VCAM-1 during the ear
ly inductive phases of DHR showed that murine IgG localized to dermal
endothelium at the site of DHR in a pattern kinetically similar to the
expression of each endothelial adhesion protein. Most importantly, th
e relative numbers of lymphocytes localized to the inflammatory site w
ere significantly reduced in DHR modified with infusions of antibodies
to either VCAM-1 or E-selectin, while the numbers of lymphocytes recr
uited to skin in the animal given F(ab')(2) fragments of an irrelevant
murine monoclonal antibody of the same isotype and at the same dose w
ere not changed. Moreover, in individual animals, the relative inhibit
ion achieved with a particular antibody was proportional to the magnit
ude of expression of the targeted adhesion protein. Therefore, both VC
AM-1 and E-selectin are functionally relevant in the genesis of cutane
ous DHR, and each appears to contribute to lymphocyte recruitment in r
elation to its relative degree of expression in any one particular ani
mal.