25% Albumin modulates adhesive interactions between neutrophils and the endothelium following shock/resuscitation.
BACKGROUND
Polymorphonuclear neutrophil (PMN) sequestration in the lung is a hallmark of acute respiratory distress syndrome (ARDS). We have shown that 25% Albumin (A25) resuscitation attenuates lung injury after hemorrhagic shock and lipopolysaccharide (LPS) exposure by reducing lung leukosequestration. We hypothesize that this protective property is mediated by alteration of neutrophil-endothelial cell adhesive interactions.


METHODS
A 2-hit rodent model of shock resuscitation was used. CD11b and L-selectin were measured using flow cytometry in rat and human neutrophils ex vivo. Intercellular adhesion molecule-1 (ICAM-1) levels were measured by Northern blot and immunohistochemistry.


RESULTS
Resuscitation with A25 attenuated the increase in PMN CD11b expression in Ringer's lactate (RL) resuscitated animals at end resuscitation and at 4-hour post-LPS. While PMN L-selectin levels remained stable in RL treated animals, A25 resuscitation resulted in a significant decrease in surface L-selectin expression at 4-hour post-LPS. ICAM-1 lung endothelial cell mRNA, was increased in RL resuscitated animals, however reduced with A25 use by 51%. The LPS induced ICAM-1 endothelial cell protein expression was also prevented with A25 resuscitation. Antioxidant property of albumin was shown to play a critical role in altering CD11b expression.


CONCLUSIONS
The A25 exerts its lung-protective activity at various levels including altering the interaction between neutrophils and endothelial cells via suppressed expression of adhesion molecules. These findings suggest a novel role for A25 as an anti-inflammatory agent in PMN-mediated diseases such as ARDS.
Powers
Kinga A
KA
Department of Surgery, University of Toronto, University Health Network, Toronto General Hospital, Ontario, Canada.
Kapus
Andras
A
Khadaroo
Rachel G
RG
Papia
Giuseppe
G
Rotstein
Ori D
OD
D000418:Albumins / Q000494:pharmacology*; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D004730:Endothelium, Vascular / Q000166:cytology* / Q000378:metabolism; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000737:chemistry / Q000378:metabolism; D019041:L-Selectin / Q000032:analysis / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D016177:Macrophage-1 Antigen / Q000032:analysis / Q000378:metabolism; D009504:Neutrophils / Q000737:chemistry / Q000166:cytology* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012128:Respiratory Distress Syndrome / Q000188:drug therapy / Q000473:pathology; D020545:Respiratory Mucosa / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D012151:Resuscitation; D012771:Shock, Hemorrhagic / Q000188:drug therapy* / Q000473:pathology; D015854:Up-Regulation / Q000187:drug effects
D000418:Albumins; D008070:Lipopolysaccharides; D016177:Macrophage-1 Antigen; D018799:Intercellular Adhesion Molecule-1; D019041:L-Selectin