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Neutrophil adhesion to fibrinogen and fibrin under flow conditions is
diminished by activation and L-selectin shedding
PH Kuijper, HI Gallardo Torres, JA van der Linden, JW Lammers, JJ Sixma, JJ Zwaginga and L Koenderman
Department of Hematology, University Hospital Utrecht, The Netherlands.
The adhesion of neutrophils (polymorphonuclear leukocytes [PMNs]) to
immobilized fibrinogen/fibrin is mediated by beta2-integrins. However, the
influence of physiologic flow conditions on neutrophil adhesion to these
surfaces is poorly defined. In this report, the effect of flow and
neutrophil activation on adhesion to immobilized fibrinogen and fibrin was
examined. For the evaluation of (the distribution of) neutrophil adhesion,
real-time video-assisted microscopy and custom- made software were used.
Under flow conditions, adherent neutrophils appeared to support the
subsequent margination of other neutrophils, thereby enhancing the
adherence of these cells to fibrin. Consequently, neutrophils adhered in
clusters, especially at higher shear stresses (eg, cluster index 1.4 at
shear 80 mPa). Preactivation of PMNs with fMLP (10(-7) mol/L) or
4beta-phorbol, 12-myristate, 13-acetate (PMA; 100 ng/mL) resulted in
approximately 50% inhibition of adhesion to fibrin and a more random
distribution (cluster index <0.5). L-selectin antibodies or
neuraminidase treatment of PMNs also inhibited adhesion and clustering,
indicating a role for L-selectin. Under static conditions, no clustering
appeared and PMN activation with fMLP or PMA caused threefold and sevenfold
increased adhesion, respectively. Under these conditions, anti-L-selectin
antibodies or neuraminidase did not affect adhesion. These results indicate
that, under flow conditions, adherent neutrophils support adhesion of
flowing neutrophils by L- selectin-mediated cell-cell interactions.
Preactivated neutrophils, with lowered L-selectin expression, are less
susceptible for this interaction. By this mechanism, adhered leukocytes can
modulate the recruitment of leukocytes to the vessel wall at sites of
inflammation.
Volume 89,
Issue 6,
pp. 2131-2138,
03/15/1997
Copyright © 1997 by The American Society of Hematology
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