Protective effects of sialylated oligosaccharides in immune complex-induced acute lung injury.
Using sialyl Lewisx (SLX) oligosaccharides derived from fucosyl transferase-expressing cells or generated synthetically, the ability of these compounds to protect against acute lung damage after deposition of immunoglobulin (Ig)G or IgA immune complexes has been determined. The synthetic compounds were tetra- and pentasaccharide derivates of SLX as well as the nonfucosylated forms of SLX as controls. In the IgG immune complex model of lung injury, which is E-selectin dependent, SLX preparations provided dose-dependent protective effects, as assessed by changes in lung vascular permeability and hemorrhage. Protective effects were associated with diminished tissue accumulation of neutrophils in lungs (as assessed by myeloperoxidase). Morphological assessment revealed reduced physical contact of neutrophils with the pulmonary vascular endothelium and reduced tissue accumulation of neutrophils. In the model of IgA immune complex-induced lung injury, which does not involve participation of neutrophils and is independent of the requirement for E-selectin, SLX preparations were not protective. These data suggest that, in neutrophil-mediated and E-selectin-dependent lung injury, SLX preparations provide significant, protective effects against inflammatory vascular injury. The ability to achieve antiinflammatory outcomes in vivo with appropriate oligosaccharides suggests a new approach to the blocking of acute inflammatory responses.
Mulligan
M S
MS
Department of Pathology, University of Michigan Medical School, Ann Arbor 48109.
Lowe
J B
JB
Larsen
R D
RD
Paulson
J
J
Zheng
Z L
ZL
DeFrees
S
S
Maemura
K
K
Fukuda
M
M
Ward
P A
PA
D000208:Acute Disease; D000818:Animals; D016466:CHO Cells; D002240:Carbohydrate Sequence; D015815:Cell Adhesion Molecules / Q000378:metabolism; D006224:Cricetinae; D019040:E-Selectin; D007105:Immune Complex Diseases / Q000276:immunology / Q000517:prevention & control*; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D008297:Male; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000096:biosynthesis / Q000737:chemistry / Q000627:therapeutic use*; D011014:Pneumonia / Q000276:immunology / Q000517:prevention & control*; D051381:Rats; D011971:Receptors, Immunologic / Q000378:metabolism; D012794:Sialic Acids / Q000737:chemistry / Q000627:therapeutic use*
D015815:Cell Adhesion Molecules; D019040:E-Selectin; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D009844:Oligosaccharides; D011971:Receptors, Immunologic; D012794:Sialic Acids