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Blood, 1 November 2005, Vol. 106, No. 9, pp. 3234-3241.
Prepublished online as a Blood First Edition Paper on July 7, 2005; DOI 10.1182/blood-2005-03-1288.
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Submitted March 29, 2005
Accepted June 28, 2005
A specific role of integrin Mac-1 in accelerated macrophage efflux to the lymphatics
Chunzhang Cao, Daniel A Lawrence, Dudley K Strickland, and Li Zhang*
Departments of Physiology and Surgery, University of Maryland School of Medicine, Rockville, MD, USA
* Corresponding author; email: LiZhang{at}SOM.UMARYLAND.EDU.
In response to injury, monocytes migrate to the site of inflammation, where they differentiate into macrophages and participate in various biological processes. However, their fate during the resolution of acute inflammation is not fully understood. Here we show that inflammatory macrophages do not die locally by apoptosis; rather, they migrate across the peritoneal mesothelium to the lymphatics, through which they further migrate to the lymph nodes and to the blood circulation. Macrophage efflux is enhanced considerably upon cell activation and such accelerated macrophage migration is dependent specifically on integrin Mac-1, and can be blocked by addition of its antagonist. Thus, genetic inactivation of Mac-1 in mice inhibits the accelerated macrophage efflux from the inflammatory site to the lymphatics, but does not compromise the accumulation of blood monocytes into the inflammatory site. Together, our study demonstrates that Mac-1 is involved specifically in the efflux of activated macrophages to the lymphatics, suggesting that Mac-1 may play an important role in the removal of local inflammatory macrophages and in their subsequent migration to the lymph nodes, a process that is critical to the development of the adaptive immunity.
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