Relationship between Plasma Fibrinogen Levels and Pulmonary Function in the Japanese Population: The Takahata Study

Background:Plasma fibrinogen is considered a biomarker of respiratory disease, owing to the relationship between plasma fibrinogen and pulmonary function established in Western populations. However, such a relationship has not yet been confirmed in an Asian population. We assessed this relationship in the general Japanese population.Methods:Totally, 3,257 men and women aged ≥40 years who participated in a community-based annual health checkup in Takahata, Japan, from 2004 to 2006, underwent spirometry, and their plasma fibrinogen levels were determined.Results:We found an inverse relationship between spirometric measures (percent predicted forced vital capacity [%FVC] and forced expiratory volume in 1s [%FEV₁], and FEV₁/FVC) and plasma fibrinogen levels in men, but not in women. The plasma fibrinogen levels were significantly higher in subjects with restrictive, obstructive, and mixed ventilatory disorders than in those with normal spirometry results. Multiple linear regression analysis revealed that in men, plasma fibrinogen levels were predictive for %FVC and %FEV₁ (independent of age, body mass index, and cigarette smoking) but not for FEV₁/FVC.Conclusions:Plasma fibrinogen was significantly associated with pulmonary function in Japanese men, and as such, plasma fibrinogen might be a potent biomarker for pulmonary dysfunction in men.     

An L-selectin ligand distinct from P-selectin glycoprotein ligand-1 is expressed on endothelial cells and promotes neutrophil rolling in inflammation

Neutrophils recruited from the blood are key players in the innate immune response. Selectins play critical roles in neutrophil recruitment by mediating their tethering and rolling in inflamed venules. While the roles of P- and E-selectin in this process are well established, the mechanisms of L-selectin-mediated neutrophil recruitment remain elusive. One proposal is that tethering is mediated by L-selectin on flowing neutrophils interacting with P-selectin glycoprotein ligand-1 (PSGL-1) on adherent neutrophils. To clarify whether L-selectin-mediated neutrophil recruitment depends entirely on PSGL-1, we examined the impact of L-selectin deficiency in mice with a PSGL-1-deficient background. L-selectin and PSGL-1 double-knockout mice exhibited a higher increase in their peripheral blood neutrophil count and a worse defect in neutrophil recruitment into the inflamed peritoneum than PSGL-1-deficient mice. Intravital microscopy of inflamed cremaster muscle venules showed that L-selectindeficiency or antibody blockade of L-selectin reduced the residual leukocyte rolling in PSGL-1-deficient mice. Flow cytometric analyses showed that the endothelial cells from the cremaster muscle bound L-selectin in a PSGL-1-independent manner. These results provide evidence for the existence of an L-selectin ligand distinct from PSGL-1 in inflammation and indicate that such a ligand is expressed on endothelial cells, promoting neutrophil rolling in vivo.