Abstract

What makes our lungs look red? This seems to be a naïve and trivial question. Indeed, all the textbooks tell us that what makes our body red is the presence of blood, or more precisely the red blood cells (RBC). Here we provide some experimental evidence as well arguments to prove that this belief is wrong, or only partially true. In fact, we identified an important population of red cells located outside of the blood vessels as highly compacted clusters, in the connection tissues of the lungs of several species of animals including rat and human being. These red cells possessed each a nucleus, expressing several biomarkers of different cell types such as PF4, vWF, SCF-1R, CD200R, TGF-b, etc. Interestingly, being morphologically heterogeneous, they react collectively to certain stimuli. For example, they aggregated on collagen fibers forming clusters of cells resembling that observed in vivo. The red cells may have some features of Hematopoietic Stem Cells, since they were capable of differentiating into other cell types such as alveolar macrophages. In nasal polyps, these cells formed vessel-like structures, confined within a CD31-positive tube. Upon exposure to toxic chemicals, they formed dense networks, suggesting a possible role in coagulation. Furthermore, the number of these red cells was greatly increased in the lungs of diseased donors, especially in the lungs of CF patients. Instead of being secreted as what happens in normal red cells, vWF proteins were tethered on the cytoplasmic membrane of the red cells isolated from the lungs of CF donors, which may explain at least partially the fibrotic nature of the CF lungs.

Taken together, we conclude that what makes the lungs look red is not the red blood cells, rather a distinct population of red cells, we call them Red Soma Cells (RSC). We believe that the discovery and characterization of this important population of cells will have profound theoretic as well as therapeutic implications.

Keywords: Stem cells; Collagen; vWF; Cystic fibrosis; Pattern formation; RBC