Community-acquired pneumonia and sepsis.

Sepsis is a frequent and often fatal complication of pneumonia. This article discusses the epidemiology, pathophysiology, and treatment of sepsis in the setting of pneumonia. Particular consideration is given to the role of mechanical ventilation in amplifying organ dysfunction in sepsis and to treatments that have positive effects on sepsis mortality and respiratory dysfunction.

S1P(4) receptor mediates S1P-induced vasoconstriction in normotensive and hypertensive rat lungs.

This study aimed to identify receptors mediating sphingosine-1-phosphate (S1P)-induced vasoconstriction in the normotensive and chronic hypoxia-induced hypertensive rat pulmonary circulation. In isolated perfused lungs from normoxic rats, infusion of S1P caused a sustained vasoconstriction, which was not reduced by combinational pretreatment with the dual S1P(1 and 3) receptor antagonist VPC23019 and the S1P(2) receptor antagonist JTE013. The S1P(4) receptor agonists phytosphingosine-1-phospate and VPC23153, but not the dual S1P(1 and 3) receptor agonist VPC24191, caused dose-dependent vasoconstrictions. In hypertensive lungs from chronically hypoxic rats, the vasoconstrictor responses to S1P and VPC23153 were markedly enhanced. The S1P(4) receptor agonist VPC 23153 caused contraction of isolated pulmonary but not of renal or mesenteric arteries from chronically hypoxic rats. S1P(4) receptor protein as well as mRNA were detected in both normotensive and hypertensive pulmonary arteries. In contrast to what has been reported in the systemic circulation and mouse lung, our findings raise the possibility that S1P(4) receptor plays a significant role in S1P-induced vasoconstriction in the normotensive and hypertensive rat pulmonary circulation.

Identification of novel resident pulmonary stem cells: form and function of the lung side population.

Resident lung stem cells function to replace all lineages of pulmonary tissue, including mesenchyme, epithelium, and vasculature. The phenotype of the lung side population (SP) cells is currently under investigation; their function is currently unknown. Recent data suggest lung SP cells are an enriched tissue-specific source of organ-specific pulmonary precursors and, therefore, a source of adult stem cells. The adult lung SP cell population has been isolated and characterized for expression of markers indicative of stem cell, epithelial, and mesenchymal lineages. These studies determined that the adult mouse lung SP has epithelial and mesenchymal potential that resides within a CD45- mesenchymal subpopulation, as well as limited hematopoietic ability, which resides in the bone marrow-derived CD45+ subpopulation. The ability to identify these adult lung precursor cells allows us to further study the potential of these cells and their role in the regulation of tissue homeostasis and response to injury. The identification of this target population will potentially allow earlier treatment and, long term, a functional restoration of injured pulmonary tissue and lung health.