Understanding the role of neutrophils in acute respiratory distress syndrome.

Acute respiratory distress syndrome (ARDS) is difficult to treat and is associated with a high mortality rate. The most severe form of coronavirus disease 2019 (COVID-19) also leads to life-threatening ARDS. Neutrophil counts are positively correlated with disease severity in ARDS. Neutrophil activation not only plays a significant role in immune defense against infections, but also causes tissue damage and leads to inflammatory diseases. Activated neutrophils rapidly migrate to inflamed lung tissue, releasing toxic granular contents and generating neutrophil extracellular traps. In the last few decades, it has become apparent that neutrophils occupy a central role in ARDS pathology. In this review, we summarize the neutrophil inflammatory responses and their relationships to ARDS. According to the current literature, understanding the function of neutrophils may be helpful in the treatment of ARDS.

YC-1 attenuates homotypic human neutrophil aggregation through inhibition of phosphodiesterase activity.

This study was undertaken to assess the effects of 3-(5'-hydroxymethyl-2'-furyl)-1-benzyl indazole (YC-1), a known activator of soluble guanylyl cyclase, on formyl-l-methionyl-l-leucyl-l-phenylalanine (FMLP) and complement component 5a (C5a)-induced homotypic human neutrophil aggregation. YC-1 as well as the phosphodiesterase (PDE)4 inhibitors rolipram and Ro 20-1724, but not the PDE3 inhibitor milrinone, inhibited the aggregation responses stimulated by FMLP and C5a. In contrast, sodium nitroprusside (SNP) had no effect on FMLP- or C5a-induced neutrophil aggregation. Moreover, SNP together with YC-1 failed to modify the YC-1-induced responses. In addition, YC-1 and rolipram, but not milrinone, induced substantial increases in cAMP levels, which occurred through the inhibition of PDE activity but not an increase in adenylate cyclase function. Interestingly, adenosine deaminase abolished the inhibitory effects and cAMP levels of YC-1, rolipram, and Ro 20-1724. In conclusion, these results indicate that the inhibitory effect of YC-1 on homotypic neutrophil aggregation is attributed to an elevation in the cAMP concentration through inhibition of the activity of PDE, which may potentiate the autocrine functions of endogenous adenosine.