Premium
Transmigrated neutrophils down‐regulate the expression of VCAM‐1 on endothelial cells and inhibit the adhesion of flowing lymphocytes
Author(s) -
Stone Philip C. W.,
Lally Frank,
Rahman Mahbub,
Smith Emily,
Buckley Christopher D.,
Nash Gerard B.,
Rainger G. Ed
Publication year - 2005
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0504304
Subject(s) - vcam 1 , cell adhesion molecule , biology , intercellular adhesion molecule 1 , cell adhesion , icam 1 , lymphocyte , microbiology and biotechnology , peripheral blood mononuclear cell , lymphocyte homing receptor , adhesion , tumor necrosis factor alpha , immunology , soluble cell adhesion molecules , cell–cell interaction , cell , in vitro , chemistry , biochemistry , organic chemistry
As the first leukocytes recruited during inflmmation, neutrophils are ideally situated to regulate the subsequent recruitment of mononuclear leukocytes. Here, we found that human neutrophils recruited by endothelial cells (EC), which had been stimulated with tumor necrosis factor α for 4 h, inhibited the adhesion of flowing, mixed mononuclear cells or purified lymphocytes over the subsequent 20 h but did not affect the adhesion of a secondary bolus of neutrophils. The degree of inhibition of lymphocyte adhesion increased with the duration of neutrophil‐EC contact and with the number of recruited neutrophils. Antibody‐blocking studies showed that lymphocyte adhesion was mediated predominantly by vascular cell adhesion molecule‐1 (VCAM‐1). Recruited neutrophils reduced the EC expression of VCAM‐1 but not intercellular adhesion molecule‐1 (ICAM‐1) or E‐selectin in a manner that mirrored the time‐ and number‐dependent reduction in lymphocyte adhesion. VCAM‐1 was not shed into the culture supernatant, and a panel of protease inhibitors was unable to reverse its down‐regulation, indicating that it was not proteolytically degraded by neutrophils. In EC that had been in contact with neutrophils, the mRNA message for VCAM‐1 but not ICAM‐1 was down‐regulated, indicating that alterations in transcriptional activity were responsible for the reduction in VCAM‐1. Thus, under some inflammatory milieu, neutrophils may delay the recruitment of mononuclear leukocytes by regulating the expression of EC adhesion receptors.