Stem cell biology in the lung and lung cancers: using pulmonary context and classic approaches.

Classic stem cell biology approaches tailored specifically with lung biology in mind are needed to bring the field of lung stem cell biology up to speed with that in other tissues. The infrequent cellular turnover, the diversity of cell types, and the necessity of daily cell function in this organ must be considered in stem cell studies. Previous work has created a base from which to explore transplantation, label retention, and more sophisticated lineage-tracing schemes to identify and characterize stem cell populations in the normal lung. These approaches are also imperative for building on precedents set in other tissues in the exploration of the cancer stem cell hypothesis in lung cancers. Additionally, recent studies provide key leads to further explore the molecular mechanisms that regulate lung homeostasis. Here, we discuss strategies to advance the field of lung stem cell biology with an emphasis on developing new, lung-specific tools.

PLA2 promotes fusion between PMN-specific granules and complex liposomes.

Neutrophil stimulation results in the activation of a variety of phospholipases, including phospholipase A2 (PLA2), which releases arachidonic acid from the 2 position of membrane phospholipids, leaving a lysophospholipid. Because arachidonic acid is known to be a potent fusogen in vitro, we examined the effect of metabolism by PLA2 on the fusion of complex liposomes (liposomes prepared with a phospholipid composition similar to that found in neutrophil plasma membrane). We observed that PLA2 augmented the fusion of complex liposomes with each other as well as with specific granules isolated from human neutrophils, lowering the Ca2+ requirement for fusion by three orders of magnitude. Furthermore, although lysophospholipids inhibited fusion, the incorporation of arachidonic acid into liposome membranes overcame the inhibitory effects of the lysophospholipids. Thus with PLA2 and annexins we were able to obtain fusion of complex liposomes at concentrations of Ca2+ that are close to physiological. Our data suggest that the activation of PLA2 and the generation of arachidonic acid may be the major fusion-promoting event mediating neutrophil degranulation.