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Brief Definitive Report |
4 Integrin in the Inflammatory Response of Neutrophils
hogg{at}icrf.icnet.uk
After injury or infection, neutrophils rapidly migrate from the circulation into tissues by means of an orderly progression of adhesion receptor engagements. Neutrophils have been previously considered to use selectins exclusively to roll on vessels before an adhesion step mediated by the β2 integrins, lymphocyte function–associated antigen (LFA)-1, and Mac-1. Here we use LFA-1–/– mice, function blocking monoclonal antibodies, and intravital microscopy to investigate the roles of LFA-1, Mac-1, and
4 integrins in neutrophil recruitment in vivo. For the first time, we show that LFA-1 makes a contribution to neutrophil rolling by stabilizing the transient attachment or tethering phase of rolling. In contrast, Mac-1 does not appear to be important for either rolling or firm adhesion, but instead contributes to emigration from the vessel. Blocking Mac-1 in the presence of LFA-1 significantly reduces emigration, suggesting cooperation between these two integrins. Low levels of 4β1 integrin can be detected on neutrophils from LFA-1+/+ and –/– mice. These cells make use of 4β1 during the rolling phase, particularly in the absence of LFA-1. Thus LFA-1 and 4β1, together with the selectins, are involved in the rolling phase of neutrophil recruitment, and, in turn, affect the later stages of the transmigration event.
Key Words: LFA-1 • integrin • rolling • neutrophils • inflammation
© 2001 The Rockefeller University Press
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