Pulmonary expression of vascular endothelial growth factor in sepsis.
BACKGROUND
Vascular endothelial growth factor (VEGF), an angiogenic and chemotactic peptide, is abundantly expressed in normal lung tissue, especially in alveolar and bronchial epithelium, glandular cells of the bronchi, and activated alveolar macrophages.


OBJECTIVE
To investigate the role of VEGF in progressively impaired lung function as the major complication and cause of death in septic patients.


METHODS
We evaluated pulmonary VEGF expression in lung autopsy material from septic patients who had been cared for by intensive care medicine using enzyme-linked immunosorbent assay (ELISA), reverse transcriptase-polymerase chain reaction (RT-PCR), and immunohistochemical methods.


RESULTS
Compared with expression in nonseptic control individuals (n = 10), pulmonary VEGF expression as determined by ELISA was significantly (P <.001) decreased in septic patients (n = 8). As monitored by RT-PCR, mRNA for the 2 splice variants, VEGF(121) and VEGF(165), and for VEGFR-2/KDR were expressed in both groups, the yields being lower in the sepsis group. Samples from septic patients lacked or showed only sparse immunoreaction on bronchial and alveolar epithelium, whereas this reaction was strong in all control samples. However, alveolar macrophages were similarly immunopositive in both groups.


CONCLUSIONS
The precise underlying mechanisms for the distinctly different expression of pulmonary VEGF in septic patients and nonseptic control individuals are not clear at present. Particularly the role of VEGF in the development of sepsis-induced lung injury and acute respiratory distress syndrome in mechanically ventilated patients suffering from severe sepsis remains to be clarified.
Tsokos
Michael
M
Institute of Legal Medicine, University of Hamburg, Germany. mtsokos@web.de
Pufe
Thomas
T
Paulsen
Friedrich
F
Anders
Sven
S
Mentlein
Rolf
R
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017398:Alternative Splicing; D001344:Autopsy; D016228:Endothelial Growth Factors / Q000096:biosynthesis* / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis* / Q000276:immunology; D008168:Lung / Q000098:blood supply / Q000737:chemistry / Q000473:pathology*; D008222:Lymphokines / Q000096:biosynthesis* / Q000276:immunology; D016676:Macrophages, Alveolar / Q000737:chemistry / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000737:chemistry / Q000473:pathology; D020033:Protein Isoforms / Q000096:biosynthesis / Q000276:immunology; D012128:Respiratory Distress Syndrome / Q000209:etiology / Q000473:pathology; D020545:Respiratory Mucosa / Q000737:chemistry / Q000473:pathology; D018805:Sepsis / Q000150:complications / Q000473:pathology*; D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000096:biosynthesis / Q000276:immunology; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D020033:Protein Isoforms; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D040301:Vascular Endothelial Growth Factor Receptor-2