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2265212 
Journal Article 
Abstract 
Pericyte-like cells are a major source of nitric oxide-sensitive guanylyl cyclase in the murine lung 
Koenig, P; Groneberg, D; Friebe, A 
2010 
Yes 
American Journal of Respiratory and Critical Care Medicine
ISSN: 1073-449X
EISSN: 1535-4970 
181 
A3435 
English 
WOS:000208771002545 
is part of a larger document 3452678 Proceedings of the American Thoracic Society 2010 International Conference, May 14-19, 2010, New Orleans
Rationale: Nitric oxide (NO) serves several important functions in the lung such as regulation of vascular tone and permeability via its receptor NO-sensitive guanylyl cyclase (NO-GC). Despite its importance for lung biology, information on the cell type(s) expressing NO-GC is lacking due to the fact that antibodies used previously to detect NO-GC were often unspecific. This study aimed to clarify this point by use of an antibody whose specificity was monitored with the help of a mouse line deficient in NO-GC β1 subunit.

Methods: We used an affinity-purified peptide antibody against the β1 subunit of NO-GC. Labeling was judged to be specific when absent in NO-GC β1 subunit-deficient animals. Immunohistochemistry was performed in murine lungs on the light and electron microscopic level and double and triple labeling in combination with appropriate cell type-specific markers were used to determine the identity of NO-GC expressing cells.

Results: As expected from functional studies, vascular smooth muscle cells exhibited NO-GC immunoreactivity. However, the highest intensity of NO-GC-immune reaction was located in the alveolar region. Immunostaining in precision cut lung slices revealed that NO-GC immunoreactivity was not located in endothelial cells, as previously reported, but was present in highly branched cells whose branches were in close contact to capillary endothelial cells. Endothelial cells themselves did not contain detectable amounts immunoreactivty for NO-GC. Close to the pleura where capillaries were more elongated as compared to the more central portions of the lung, NO-GC-immunoreactive cells encompassed endothelial cells and had the classical morphology of endothelial cells. Preembedding immuno-electron microscopy confirmed that NO-GC-immunoreactive processes were indeed in close apposition to endothelial cells as would be expected from pericytes. Double labeling-immunohistochemistry revealed that NO-GC immunoreactive cells were also immunoreactive for other downstream components of the NO-GC pathway such as vasodilator-stimulated phosphoprotein (VASP) and phosphodiesterase 5 (PDE5).

Conclusion: These results show that in the alveolar region, NO-GC is predominantly expressed in pericyte-like cells and co-localizes with other parts of the NO-GC signal transduction machinery making them prime candidates to regulate capillary permeability in the alveolar region. 
American Thoracic Society 2010 International Conference 
New Orleans, LA 
May 14-19, 2010