Recognition of a consensus carbohydrate structure in the ligands
for selectins (cd62s) by a novel antibody against sialyl lewis x in
vitro and in vivo.
Tamatani, Takuya, Makoto Suematsu, Katsunari Tezuka, Naomi Hanzawa,
Tsutomu Tsuji, Yuzuru Ishimura, Reiji Kannagi, Satoshi Toyoshima, and
Mitsuo Homma.
Pharmaceutical Basic Research Laboratories, Japan Tobacco Inc., 1
-13-2 Fukuura, Kanazawa-ku, Yokohama 236, JAPAN; Department of
Biochemistry, School of Medicine, Keio University, 35 Shinano-machi,
Shinjuku-ku, Tokyo 160, JAPAN; Laboratory of Experimental Pathology,
Aichi Cancer Center, Research Institute, 1-1 Kanoko-den, Chikusa-ku,
Nagoya 464, JAPAN; Division of Chemical Toxicology and
Immunochemistry, Faculty of Pharmaceutical Science, The University of
Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113, JAPAN
APStracts 2:0171H, 1995.
The selectins (L,E and P) play an important role in the earliest
events of the inflammatory response, leading to the "rolling"
phenomenon. All selectins react with sialyl Lewis X (SLex) in vitro,
possibly suggesting that their ligands have a consensus structure.
2H5 is a monoclonal antibody against SLex, that blocks L-selectin
-mediated adhesion. 2H5 inhibited adhesion of HL60 cells to P- and E
-selectin-producing COS cells in vitro and immunoprecipitated a PSGL
-1-like glycoprotein from HL60 cell lysate, suggesting that it
recognizes a functional consensus structure on the ligands for all
selectins. 2H5 reacted not only with human but also with rat and
mouse neutrophils. 2H5 is the first antibody against SLex that
recognizes neutrophils of non-human mammals. The carbohydrate
structure recognized by 2H5 was present not only on high endothelial
venules of rat lymphoid organs, but also on the endothelial cells of
non-lymphoid organs. Furthermore, administration of the antibody
markedly inhibited L- and P-selectin-mediated neutrophil rolling and
adhesion in rat mesenteric venules in vivo. These results provide
evidence for the presence of a consensus carbohydrate structure on
the ligands for all selectins. The consensus structure thus has the
potential to serve as a therapeutic target.
Received 10 February 1995; accepted in final form 14 April 1995.
APS Manuscript Number H91-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 2 May 1995.