Background and purpose: The serine protease neutrophil elastase (NE) appears to regulate inflammatory responses at multiple levels but its role in leukocyte transmigration in vivo remains unclear. The present study aimed to address this issue by using both an NE inhibitor (ONO-5046) and NE deficient (NEExperimental approach: A number of inflammatory mediators (LTB 4 , KC and PAF) were investigated in vitro for their ability to stimulate the release and the surface expression of NE by neutrophils. In addition, the role of NE in leukocyte migration elicited by topical LTB 4 was investigated in vivo in mouse cremasteric venules as observed by intravital microscopy. Key results: Amongst the mediators tested in vitro, LTB 4 was found to be a highly potent and efficacious inducer of NE cell surface expression on murine neutrophils. Furthermore, in wild-type mice (WT), LTB 4 -induced leukocyte transmigration was reduced by intravenous ONO-5046 (66% inhibition), an effect that appeared to occur at the level of the perivascular basement membrane. Interestingly, LTB 4 -induced responses were normal in NE À/À mice and, while ONO-5046 had no inhibitory effect in these animals, the broad-spectrum serine protease inhibitor aprotinin suppressed leukocyte transmigration in both WT and NE À/À mice. Conclusions and implications:The findings demonstrate the potent ability of LTB 4 to induce cell-surface expression of NE and provide evidence for the involvement of NE in LTB 4 -induced neutrophil transmigration in vivo. The results also suggest the existence of compensatory mechanisms in NE À/À mice, highlighting the added value of investigating pharmacological blockers in parallel with genetic deletion.

It is challenging to identify metrics that best capture hurricane destructive potential and costs. Although it has been found that the sea surface temperature and vertical wind shear can both make considerable changes to the hurricane destructive potential metrics, it is still unknown which plays a more important role. Here we present a new method to reconstruct the historical wind structure of hurricanes that allows us, for the first time, to calculate the correlation of damage with integrated power dissipation and integrated kinetic energy of all hurricanes at landfall since 1988. We find that those metrics, which include the horizontal wind structure, rather than just maximum intensity, are much better correlated with the hurricane cost. The vertical wind shear over the main development region of hurricanes plays a more dominant role than the sea surface temperature in controlling these metrics and therefore also ultimately the cost of hurricanes.

In this study, we show that the number of annual global tropical cyclone (TC) landfalls with major landfall intensity (LI ≥ 50 m s−1) has nearly doubled from 1982 to 2020. The lifetime maximum intensity (LMI) of global major landfalling TCs has been increasing by 0.8 m s−1 per decade (p < 0.05), but this significance of intensity change disappears at landfall (0.3 m s−1 per decade, p = 0.69). The lack of a significant LI trend is caused by the much larger variance of LI than that of LMI in all basins and explains why a significant count change of TCs with major intensity at landfall has only now emerged. Basin-wide TC trends of intensity and spatial distribution have been reported, but this long-term major TC landfall count change may be the most socio-economic significant.

It remains unclear how tropical cyclones (TCs) decay from their ocean lifetime maximum intensity (LMI) to landfall intensity (LI), yet this stage is of fundamental importance governing the socio-economic impact of TCs. Here we show that TCs decay on average by 25% from LMI to LI. A logistic decay model of energy production by ocean enthalpy input and surface dissipation by frictional drag, can physically connect the LMI to LI. The logistic model fits the observed intensity decay as well as an empirically exponential decay does, but with a clear physical foundation. The distance between locations of LMI and TC landfall is found to dominate the variability of the decay from the LMI to LI, whereas environmental conditions are generally less important. A major TC at landfall typically has a very large LMI close to land. The LMI depends on the heating by ocean warming, but the LMI location is also important to future landfall TC intensity changes which are of socio-economic importance.