In vivo e-selectin upregulation correlates early with infiltration
of pmn, later with pbl-entry: mabs block both.
Binns, Richard M, Stephen T Licence, Andrew A Harrison, Edward T D
Keelan, Martyn K Robinson, and Dorian O Haskard.
Department of Immunology, The Babraham Institute, Cambridge CB2
4AT; Rheumatology Unit, Department of Medicine, Royal Postgraduate
Medical School, Hammersmith Hospital, London W12 ONN and Celltech
Research, Celltech Ltd., Slough, SL1 4EN
APStracts 2:0285H, 1995.
The endothelial molecule E-selectin binds most leukocyte subsets in
vitro. Yet its role in regulating the very different kinetics of
inflammatory infiltration of different leukocyte subsets in vivo is
unclear. The kinetics of E-selectin upregulation and polymorph (PMN)
and blood lymphocyte (PBL) localization in inflammation induced by
interleukin 1 (IL-1[alpha]), tumor necrosis factor (TNF[alpha]),
phytohemagglutinin (PHA) and phorbol myristate acetate (PMA) were
investigated in a well-established inbred pig trafficking model. They
differed markedly both for these three labeled indicators of
inflammation and in each of the four inflammatory processes. In each,
E-selectin upregulation correlated with early PMN entry and later
with PBL infiltration but was more protracted than both. The
importance of E-selectin was confirmed by marked inhibition of PMN
and PBL entry (up to >60%) by F(ab')2 anti-E-selectin.
Involvement of other molecules was illustrated by similar or greater
inhibition with anti-CD18 F(ab')2. We conclude that, like CD18, E
-selectin is necessary for most PMN and PBL infiltration but alone is
insufficient, consistent with the involvement of several alternative
multistep molecular mechanisms in this entry.
Received 28 February 1995; accepted in final form 26 June 1995.
APS Manuscript Number H196-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 18 July 1995.