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Global vascular expression of murine CD34, a sialomucin-like endothelial
ligand for L-selectin
S Baumhueter, N Dybdal, C Kyle and LA Lasky
Department of Immunology, Genentech, Inc, San Francisco, CA 94080.
Extravasation of leukocytes into organized lymphoid tissues and into sites
of inflammation is critical to immune surveillance. Leukocyte migration to
peripheral lymph nodes (PLN), mesenteric lymph nodes (MLN) and Peyer's
patches (PP) depends on L-selectin, which recognizes carbohydrate-bearing,
sialomucin-like endothelial cell surface glycoproteins. Two of these
ligands have been identified at the molecular level. One is the potentially
soluble mucin, GlyCAM 1, which is almost exclusively produced by high
endothelial venules (HEV) of PLN and MLN. The second HEV ligand for
L-selectin is the membrane-bound sialomucin CD34. Historically, this
molecule has been successfully used to purify human pluripotent bone marrow
stem cells, and limited data suggest that human CD34 is present on the
vascular endothelium of several organs. Here we describe a comprehensive
analysis of the vascular expression of CD34 in murine tissues using a
highly specific antimurine CD34 polyclonal antibody. CD34 was detected on
vessels in all organs examined and was expressed during pancreatic and skin
inflammatory episodes. A subset of HEV-like vessels in the inflamed
pancreas of nonobese diabetic (NOD) mice are positive for both CD34 and
GlyCAM 1, and bind to an L-selectin/immunoglobulin G (IgG) chimeric probe.
Finally, we found that CD34 is present on vessels of deafferentiated PLN,
despite the fact that these vessels are no longer able to interact with
L-selectin or support lymphocyte binding in vitro or trafficking in vivo.
Our data suggest that the regulation of posttranslational carbohydrate
modifications of CD34 is critical in determining its capability to act as
an L-selectin ligand. Based on its ubiquitous expression, we propose that
an appropriately glycosylated form of vascular CD34 may act as a ligand for
L-selectin-mediated leukocyte trafficking to both lymphoid and nonlymphoid
sites.
Volume 84,
Issue 8,
pp. 2554-2565,
10/15/1994
Copyright © 1994 by The American Society of Hematology
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