Dipeptidyl peptidase I (DPPI) is a lysosomal cysteine protease critical for the activation of granule-associated serine proteases, including neutrophil elastase, cathepsin G, and proteinase 3. DPPI and granule-associated serine proteases have been shown to play a key role in regulating neutrophil recruitment at sites of inflammation. It has recently been suggested that neutrophils and neutrophil-associated proteases may also be important in the development and progression of abdominal aortic aneurysms (AAAs), a common vascular disease associated with chronic inflammation and destructive remodeling of aortic wall connective tissue. Here we show that mice with a loss-of-function mutation in DPPI are resistant to the development of elastase-induced experimental AAAs. This is in part because of diminished recruitment of neutrophils to the elastase-injured aortic wall and impaired local production of CXC-chemokine ligand (CXCL) 2. Furthermore, adoptive transfer of wild-type neutrophils is sufficient to restore susceptibility to AAAs in DPPI-deficient mice, as well as aortic wall expression of CXCL2. In addition, in vivo blockade of CXCL2 by using neutralizing antibodies directed against its cognate receptor leads to a significant reduction in aortic dilatation. These findings suggest that DPPI and/or granule-associated serine proteases are necessary for neutrophil recruitment into the diseased aorta and that these proteases act to amplify vascular wall inflammation that leads to AAAs. cardiovascular ͉ inflammation ͉ innate immunity ͉ proteases

Importance Electronic cigarette (e-cigarette) use in pregnancy has been steadily increasing and has been hyped as being a safe alternative to cigarette smoking during pregnancy. This review discloses what is currently known about e-cigarette use in pregnancy and the effects of its use on pregnancy outcomes. Objective To determine what is currently known about the prevalence of e-cigarette use in pregnancy and the effects of e-cigarette use on pregnancy and perinatal/neonatal outcomes. Evidence Acquisition A PubMed, CINAHL, and EMBASE search was undertaken using the search terms “pregnancy” OR “pregnancy complications” OR “pregnancy outcome” OR “newborn” OR “neonate” OR “birth” AND “electronic cigarettes” OR “e-cigarettes” OR “ecigarettes” OR “vaping” OR “vape.” The search was limited to the English language and between 2007 and October 12, 2017. Results The search identified 91 articles, 40 of which are the basis for this review. The prevalence of e-cigarette use is 0.6% to 15%. The amount of nicotine consumed by e-cigarette users is comparable to that consumed by cigarette smokers. Most of the animal model studies suggest a potential danger to the developing fetus primarily because of the nicotine consumed and that consumption has multiple effects on the immune system, neural development, lung function, and cardiac function. There is a widespread flawed perception that e-cigarettes are safe to use during pregnancy. Conclusions The marketing of e-cigarette use as a safer alternative to cigarette smoking has led to an increasing use even in pregnancy. The nicotine consumed by e-cigarettes is similar to that consumed by cigarette smoking. Animal studies confirm the dangers of nicotine to the developing fetus. More research needs to be done specifically assessing e-cigarette use, pregnancy, and pregnancy outcomes. Relevance The amount of nicotine consumed in cigarette smoking is similar to the amount of nicotine consumed with e-cigarettes. The effects of nicotine exposure during fetal development are well known and include effects on multiple organ systems. Target Audience Obstetricians and gynecologists, family physicians. Learning Objectives After completing this activity, the learner should be better able to determine the prevalence of e-cigarette use in pregnancy, analyze and compare the nicotine consumed with cigarette smoking versus the nicotine consumed with e-cigarette smoking, and evaluate the risk in animal studies of the consumption of nicotine on the developing fetus.

The polymorphonuclear leukocyte (PMN)-derived serine proteases play a key role in immune complex (IC)-mediated inflammation. However, the mechanisms by which these proteases regulate inflammatory response remain largely undefined. Here, we show that IC-activated cathepsin G- and neutrophil elastase-deficient (CG/NE) PMNs adhered normally to IC-coated surfaces but did not undergo CD11b clustering and failed to initiate cytoskeletal reorganization and cell spreading. As a result, CG/NE-deficient PMNs exhibited severe defects in MIP-2 secretion and reactive oxygen intermediates production. Exogenously added CG, but not proteolytically inactive CG, was sufficient to restore these defects. These findings identify an important role for CG in integrin-dependent PMN effector functions that are separate from and downstream of integrin-dependent adhesion.

The role of innate immunity in the pathogenesis of asthma is unclear. Although increased presence of neutrophils is associated with persistent asthma and asthma exacerbations, how neutrophils participate in the pathogenesis of asthma remains controversial. In this study, we show that the absence of dipeptidyl peptidase I (DPPI), a lysosomal cysteine protease found in neutrophils, dampens the acute inflammatory response and the subsequent mucous cell metaplasia that accompanies the asthma phenotype induced by Sendai virus infection. This attenuated phenotype is accompanied by a significant decrease in the accumulation of neutrophils and the local production of CXCL2, TNF, IL-1β, and IL-6 in the lung of infected DPPI−/− mice. Adoptive transfer of DPPI-sufficient neutrophils into DPPI−/− mice restored the levels of CXCL2 and enhanced cytokine production on day 4 postinfection and subsequent mucous cell metaplasia on day 21 postinfection. These results indicate that DPPI and neutrophils play a critical role in Sendai virus-induced asthma phenotype as a result of a DPPI-dependent neutrophil recruitment and cytokine response.

The use of color Doppler sonography leads to the overdiagnosis of low AFVs and does not appear to increase the detection of pregnancies destined for adverse intrapartum or perinatal outcomes.