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L-selectin can mediate leukocyte rolling in untreated mesenteric venules in
vivo independent of E- or P-selectin
K Ley, TF Tedder and GS Kansas
Freie Universitat Berlin, Department of Physiology, Germany.
Granulocyte recruitment during the acute inflammatory response is initiated
by their rolling along the endothelial lining of postcapillary venules. To
determine whether expression of L-selectin alone is sufficient for rolling,
the murine pre-B lymphocytic cell line 300.19, which does not bind E- or
P-selectin, was transfected with human L-selectin cDNA, which led to stable
L-selectin expression at a level similar to that of blood lymphocytes.
Fluorescent-labeled cells were infused retrogradely into a side branch of
the superior mesenteric artery of anesthetized rats. In venules of the
mesenteric membrane, leukocyte rolling occurs without intentional
stimulation. On average, 17% +/- 6% of L-selectin transfectants rolled in
the observed venules, while mock-transfected cells did not roll. Rolling of
L-selectin transfectants began approximately 20 minutes after surgery and
continued for at least 120 minutes. In contrast, HL-60 promyelocytes, which
express sialyl-Lewis(x) tetrasaccharide (sLe(x)) but not L- selectin and
that bind to E- and P-selectin in vitro, did not roll between 20 and 120
minutes, but some HL-60 cells rolled at very early (< 20 minutes) and
late (> 2 hours) time points. Pretreatment with either of two
function-blocking monoclonal antibodies recognizing the lectin domain of
L-selectin completely blocked rolling of L-selectin transfectants and
sharply reduced (by 70%) rolling of isolated human granulocytes. Taken
together, these results show that L-selectin can mediate leukocyte rolling
by virtue of its lectin activity.
Volume 82,
Issue 5,
pp. 1632-1638,
09/01/1993
Copyright © 1993 by The American Society of Hematology
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