Alterations in the human lung proteome with lipopolysaccharide.
BACKGROUND
Recombinant human activated protein C (rhAPC) is associated with improved survival in high-risk patients with severe sepsis; however, the effects of both lipopolysaccharide (LPS) and rhAPC on the bronchoalveolar lavage fluid (BALF) proteome are unknown.


METHODS
Using differential in gel electrophoresis (DIGE) we identified changes in the BALF proteome from 10 healthy volunteers given intrapulmonary LPS in one lobe and saline in another lobe. Subjects were randomized to pretreatment with saline or rhAPC.


RESULTS
An average of 255 protein spots were detected in each proteome. We found 31 spots corresponding to 8 proteins that displayed abundance increased or decreased at least 2-fold after LPS. Proteins that decreased after LPS included surfactant protein A, immunoglobulin J chain, fibrinogen-gamma, alpha1-antitrypsin, immunoglobulin, and alpha2-HS-glycoprotein. Haptoglobin increased after LPS-treatment. Treatment with rhAPC was associated with a larger relative decrease in immunoglobulin J chain, fibrinogen-gamma, alpha1-antitrypsin, and alpha2-HS-glycoprotein.


CONCLUSIONS
Intrapulmonary LPS was associated with specific protein changes suggesting that the lung response to LPS is more than just a loss of integrity in the alveolar epithelial barrier; however, pretreatment with rhAPC resulted in minor changes in relative BALF protein abundance consistent with its lack of affect in ALI and milder forms of sepsis.
Department of Medicine, National Jewish Health, Denver, Colorado, USA. BowlerR@njhealth.org
Russell P
RP
Bowler
Nichole
N
Reisdorph
Richard
R
Reisdorph
Edward
E
Abraham
D000328:Adult; D000418:Albumins / Q000378:metabolism; D001798:Blood Proteins / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology*; D004347:Drug Interactions; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D006242:Haptoglobins / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D007144:Immunoglobulin J-Chains / Q000378:metabolism; D008070:Lipopolysaccharides / Q000008:administration & dosage*; D008297:Male; D011486:Protein C / Q000008:administration & dosage*; D020543:Proteome / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D037662:Pulmonary Surfactant-Associated Protein A / Q000378:metabolism; D011994:Recombinant Proteins / Q000008:administration & dosage; D055815:Young Adult; D000515:alpha 1-Antitrypsin / Q000378:metabolism; D060749:alpha-2-HS-Glycoprotein
C556354:AHSG protein, human; D000418:Albumins; D001798:Blood Proteins; D006242:Haptoglobins; D007074:Immunoglobulin G; D007144:Immunoglobulin J-Chains; D008070:Lipopolysaccharides; D011486:Protein C; D020543:Proteome; D037662:Pulmonary Surfactant-Associated Protein A; D011994:Recombinant Proteins; D000515:alpha 1-Antitrypsin; D060749:alpha-2-HS-Glycoprotein; D005340:Fibrinogen