Monosodium urate crystals promote neutrophil adhesion via a cd18
-independent and selectin-independent mechanism.
Reinhardt, Paul H., Paul H. Naccache, Patrice E. Poubelle, Rinaldo De
M[acute]edicis, Marcus E. Kehrli, Jr, and Paul Kubes.
Department of Medical Physiology, University of Calgary and Centre
de Recherche en Inflammation, Immunologie et Rhumatologie, le Centre
de recherche du CHUL, Universit[acute]e Laval, Ste-Foy,
Qu[acute]ebec, GIV 4G2 and Unit[acute]e des Maladies Rhumatismales,
CHUS, Sherbrooke, Qu[acute]e, J1H 5N4 and National Animal Disease
Center, United States Department of Agriculture, Agricultural
Research
APStracts 2:0231C, 1995.
The primary objective of this study was to determine whether MSU
crystals induced neutrophil adhesion to cellular substrata and if so,
then to elucidate the molecular mechanisms involved. Human umbilical
vein endothelial cells (HUVECs) as well as various other cellular
substrata were treated with various sized MSU crystals, washed and
then co-incubated in the presence of neutrophils for 60 min. HUVECs
exposed to MSU crystals but not to silica crystals or uric acid
promoted neutrophil adhesion in a dose- and size-dependent manner, an
event also observed with monolayers of rabbit synovial cells and rat
intestinal epithelial cells. The increased neutrophil adhesion could
not be attenuated by anti-CD18, anti-ICAM-1, or various anti-selectin
antibodies despite the fact that scanning electron microscopy
revealed that neutrophils were adhering primarily to the endothelial
cells rather than exposed crystals. CD18-deficient neutrophils
adhered to MSU crystal-treated HUVEC as effectively as their CD18
positive counterparts. The neutrophil adhesion was temperature
-dependent but did not require protein synthesis. Additionally, HUVEC
phagocytosis of crystals was necessary for subsequent neutrophil
-endothelial cell interactions to transpire. Pretreatment of
endothelial cells and neutrophils with colchicine significantly
reduced the adhesive interaction. Our data demonstrate that exposure
of endothelial and other cells to MSU crystals promotes neutrophil
adhesion that occurs by a firm CD18-independent and selectin
-independent, adhesive mechanism.
Received 10 January 1995; accepted in final form 5 June 1995.
APS Manuscript Number C20-5.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 6 July 1995.