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Blood, 1 May 2006, Vol. 107, No. 9, pp. 3593-3599.
Prepublished online as a Blood First Edition Paper on January 17, 2006; DOI 10.1182/blood-2005-09-3695.
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Submitted September 14, 2005
Accepted December 15, 2005
Shedding of lymphocyte function-associated antigen (LFA)-1 in a human inflammatory response
Betsy J Evans, Alison McDowall, Peter C Taylor, Nancy Hogg, Dorian O Haskard*, and R C Landis
Eric Bywaters Centre for Vascular Inflammation, Faculty of Medicine, Imperial College London, Hammersmith Hospital, London, United Kingdom
Leukocyte Adhesion Laboratory, Cancer Research UK, London, United Kingdom
Kennedy Institute for Rheumatology, Faculty of Medicine, Imperial College London, London, United Kingdom
* Corresponding author; email: d.haskard{at}imperial.ac.uk.
Shedding of adhesion molecules has been described for members of the selectin and immunoglobulin superfamilies, but integrins are not known to be shed. Here we describe shedding of the integrin lymphocyte function-associated antigen (LFA)-1 (CD11a/CD18) from human leukocytes during the cutaneous inflammatory response to the blistering agent cantharidin. Expression of LFA-1 was significantly diminished on blister-infiltrated neutrophils (P< 0.0001) and monocytes (P=0.02) compared to cells in peripheral blood, but expression on lymphocytes remained unchanged. A capture ELISA indicated that LFA-1 was shed into blister fluid as a heterodimer expressing an intact headpiece with I and I-like epitopes. However, a CD11a central region epitope, G25.2, was absent and this remained expressed as a "stub" on the cell surface of blister neutrophils. Western analysis of soluble LFA-1 revealed a truncated 110 kDa CD11a chain and a minimally truncated 86 kDa CD18 chain. However LFA-1 was shed in a ligand-binding conformation, since it expressed KIM-127 and 24 activation epitopes and bound to solid phase ICAM-1. Shed LFA-1 was also detected in a synovial effusion by ELISA and Western analysis. We hypothesize that LFA-1 shedding may play a role in leukocyte detachment after transendothelial migration and in regulating integrin-dependent outside-in signaling.

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