Ac. Issekutz et al., CD11 CD18-INDEPENDENT TRANSENDOTHELIAL MIGRATION OF HUMAN POLYMORPHONUCLEAR LEUKOCYTES AND MONOCYTES - INVOLVEMENT OF DISTINCT AND UNIQUE MECHANISMS/, Journal of leukocyte biology, 57(4), 1995, pp. 553-561
Monocytes and polymorphonuclear leukocytes (PMNLs) migrate across cyto
kine (interleukin-1, tumor necrosis factor) activated endothelium or u
nstimulated endothelium in response to chemotactic factors in vitro an
d in vivo utilizing the CD11/CD18 (i.e., beta(2) integrin) adhesion mo
lecule complex. However, in vivo studies have suggested that under som
e conditions and/or in certain tissues, leukocyte migration can also p
roceed via CD11/CD18-independent mechanisms, Here we compared adhesion
mechanisms involved in the migration of Cr-51-labeIed blood monocytes
and PMNLs across human umbilical vein endothelium (HUVE) monolayers,
We observed that monocyte transendothelial migration was not inhibited
by monoclonal antibody (mAb) to CD18, when the HUVE was activated wit
h IL-1 and the chemotactic factor C5a induced the migration, This CD18
-independent monocyte migration,vas blocked by treatment of the monocy
te with mAb to beta 1 or alpha(4). integrin, suggesting that very late
activation antigen 4 (VLA-4) on the monocyte served as the alternativ
e migration mechanism, In contrast to monocytes, mAb to CD18 inhibited
PMNL migration to C5a across IL-1-activated HUVE, but only by 66%, si
gnificantly less than with C5a alone (84%) or IL-1-activated HUVE alon
e (95%), The migration of anti-CD18 mAb-treated PMNLs was not inhibite
d by function-blocking mAbs to sialyl Lewis(x), L-selectin, beta(1) or
alpha(4) integrin, the beta(3)-related leukocyte response integrin, I
L-8, or platelet-activating factor (PAF) antagonists, alone or in comb
ination. Antibody-blocking: studies of the ligands on HUVE indicated t
hat E-selectin may be partially involved in this CD18-independent PMNL
migration but that ICAM-1, VCAM-1, PECAM-1, and P-selectin are not in
volved. Of several chemotactic factors tested, C5a and C5a(desArg) in
activated plasma were the most active in inducing CD18-independent mig
ration of PMNLs across IL-1-activated HUVE, These results demonstrate
that (1) monocytes can utilize VLA-4 for optimal transendothelial migr
ation and (2) PMNLs may have a novel CD18-independent migration mechan
ism that is activated by C5a in conjunction with one or more ligands o
n cytokine-activated endothelium. This may involve, in part, E-selecti
n interacting with a yet to be identified counterreceptor on PMNLs.