Sialyl Lewis(x) hybridized complement receptor type 1 moderates acid aspiration injury.
The potentially enhanced anti-inflammatory effects of the sialyl Lewis(x) (sLe(x))-decorated version of soluble complement receptor type 1 (sCR1) in moderating acid aspiration injury are examined. HCl was instilled in tracheostomy tubes placed in mice, and extravasation of (125)I-labeled albumin in bronchoalveolar lavage (BAL) fluid was used to calculate the vascular permeability index (PI). Neutrophil counts in BAL fluid and immunohistochemistry were performed. PI was moderated by 82% after treatment with sCR1sLe(x) compared with 54% in sCR1-untreated mice (P < 0.05). Respective reductions in PI in mice treated 0.5 and 1 h after acid aspiration with sCR1sLe(x) of 70 and 57% were greater than the decreases in PI of 45 and 38% observed in respective sCR1-treated groups (P < 0.05). BAL fluid neutrophil counts in sCR1sLe(x)-treated mice were significantly less than those in sCR1-treated animals, which were similar to those in untreated mice. Immunohistochemistry stained for sCR1 only on the pulmonary vascular endothelium of sCR1sLe(x)- but not sCR1-treated mice. In conclusion, sCR1sLe(x) moderates permeability by antagonizing complement activation and neutrophil adhesion. Delayed complement and neutrophil antagonism significantly reduces injury.
Kyriakides
C
C
Department of Surgery, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
Wang
Y
Y
Austen
W G
WG
Favuzza
J
J
Kobzik
L
L
Moore
F D
FD
Hechtman
H B
HB
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects / Q000276:immunology; D003167:Complement Activation / Q000187:drug effects; D003169:Complement Inactivator Proteins / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000737:chemistry / Q000378:metabolism; D006851:Hydrochloric Acid; D007150:Immunohistochemistry; D008168:Lung / Q000098:blood supply / Q000737:chemistry / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000166:cytology; D009844:Oligosaccharides / Q000494:pharmacology*; D011015:Pneumonia, Aspiration / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism*; D011951:Receptors, Complement / Q000032:analysis / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D019087:Selectins / Q000378:metabolism; D000080506:Sialyl Lewis X Antigen
D003169:Complement Inactivator Proteins; D009844:Oligosaccharides; D011951:Receptors, Complement; D011994:Recombinant Proteins; D019087:Selectins; D000080506:Sialyl Lewis X Antigen; D006851:Hydrochloric Acid