Shedding of lymphocyte function-associated antigen-1 (LFA-1) in a human inflammatory response.
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-1 (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 < .001) and monocytes (P = .02) compared with cells in peripheral blood, but expression on lymphocytes remained unchanged. A capture enzyme-linked immunosorbent assay (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.
Evans
Betsy J
BJ
BHF Cardiovascular Medicine Unit, Faculty of Medicine, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN, United Kingdom.
McDowall
Alison
A
Taylor
Peter C
PC
Hogg
Nancy
N
Haskard
Dorian O
DO
Landis
R Clive
RC
D001768:Blister / Q000276:immunology / Q000473:pathology; D040881:CD11a Antigen / Q000378:metabolism; D018821:CD18 Antigens / Q000378:metabolism; D002465:Cell Movement; D019281:Dimerization; D006801:Humans; D007249:Inflammation / Q000276:immunology* / Q000473:pathology; D016023:Integrins / Q000378:metabolism; D007962:Leukocytes / Q000276:immunology / Q000473:pathology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000737:chemistry / Q000378:metabolism*; D009504:Neutrophils / Q000276:immunology / Q000473:pathology
D040881:CD11a Antigen; D018821:CD18 Antigens; D016023:Integrins; D016169:Lymphocyte Function-Associated Antigen-1