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Vol. 10, Issue 4, 861-873, April 1999
2 Integrins
Lymphocyte Function-associated Antigen-1 and Mac-1 by
Chemokines Mediated by Distinct Pathways via the 
Subunit
Cytoplasmic Domains
and
*Institut für Prophylaxe der Kreislaufkrankheiten,
Ludwig-Maximilians-Universität, D-80336 München, Germany;
and We show that CC chemokines induced a sustained
increase in monocyte adhesion to intercellular adhesion
molecule-1 that was mediated by Mac-1 (Division of Rheumatology, Immunology and Allergy,
Brigham and Women's Hospital, Harvard Medical School, Boston,
Massachusetts 02115
M
2) but not
lymphocyte function-associated antigen-1 (LFA-1; L2). In
contrast, staining for an activation epitope revealed a rapid and
transient up-regulation of LFA-1 activity by monocyte chemotactic
protein-1 (MCP-1) in monocytes and Jurkat CCR2 chemokine receptor
transfectants or by stromal-derived factor-1 in Jurkat cells.
Differential kinetics for activation of Mac-1 (sustained) and LFA-1
(transient) avidity in response to stromal-derived factor-1 were
confirmed by expression of M or L in L-deficient Jurkat cells.
Moreover, expression of chimeras containing L and M cytoplasmic
domain exchanges indicated that cytoplasmic tails conferred the
specific mode of regulation. Coexpressing M or chimeras in mutant
Jurkat cells with a "gain of function" phenotype that results in
constitutively active LFA-1 demonstrated that Mac-1 was not
constitutively active, whereas constitutive activity was mediated via
the L cytoplasmic tail, implying the presence of
distinct signaling pathways for LFA-1 and Mac-1. Transendothelial
chemotaxis of monocytes in response to MCP-1 was dependent on LFA-1;
however, Mac-1 was involved at MCP-1 concentrations stimulating its
avidity, showing differential contributions of 2 integrins.
Our data suggest that a specific regulation of 2 integrin
avidity by chemokines may be important in leukocyte extravasation and
may be triggered by distinct activation pathways transduced via the subunit cytoplasmic domains.
Corresponding author. E-mail
address: christian.weber{at}klp.med.uni-muenchen.de.
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