Neutral proteases of human polymorphonuclear granulocytes: putative mediators of pulmonary damage.

Tissue proteolytic enzymes are currently believed to be critical to the pathogenesis of panacinar emphysema. Polymorphonuclear leukocytes (Polys) have several enzymes including elastase and cathepsin G in their azurophil granules. They have collagenase in their specific granules. We have found that this collagenase is doubly latent. It has the lysosomal type of latency that depends on the impermeability of the unit membrane that surrounds each specific granule. In addition it has a latency that is converted to activity by proteolytic enzymes. The cathepsin G of the azurophil granule is a potent activator of this latent collagenase once the collagenase is released from its membrane dependent latency. Thus latency of enzymes, the nature of the latency and accessibility of the latent enzymes to activating mechanisms must all be taken into account in any analysis of their contribution to pathogenesis of local lung disease. Equally important is that fact that polys are not a prominent cellular component of normal lung. Polys must be attracted to the lung by chemotactic peptides. These peptides must be released by the interaction of inflammatory stimuli, such as smoke particles, with complement components or they must be provided by other sources. The hypothesis that lung damage in panacinar emphysema is mediated by polys and their proteases is attractive and suggestive evidence supporting this is available. However, more evidence that takes into full account the cell biology of the proteases any poly turnover in the lung are needed to extend the hypothesis and to form a rational basis for therapeutic and prophylactic measures

Smoking cessation is associated with lower rates of mood/anxiety and alcohol use disorders

BACKGROUND: The psychological outcomes that accompany smoking cessation are not yet conclusive but positive outcomes could help to persuade quitting. METHOD: We use data from the longitudinal National Epidemiological Study of Alcohol and Related Conditions. Logistic regression was used to examine associations between cigarette smoking reduction and Wave 2 status of addiction/mental health disorder among daily smokers at Wave 1, stratified by status of the diagnosis of interest at Wave 1. We adjusted for differences in baseline covariates between smokers with different levels of smoking reduction between Wave 1 and Wave 2 using propensity score regression adjustment. RESULTS: After adjusting for propensity scores and other mental health/addiction comorbidities at Wave 2, among daily smokers who had current or lifetime history diagnosis of the outcome of interest at Wave 1, quitting by Wave 2 predicted a decreased risk of mood/anxiety disorder (aOR 0.6, 95% CI 0.4, 0.9) and alcohol disorder (aOR 0.7, 95% CI 0.5, 0.99) at Wave 2. Among daily smokers with no lifetime history diagnosis of the outcome of interest at Wave 1, quitting smoking by Wave 2 predicted a decreased risk of drug use disorder at Wave 2 aOR 0.3, 95% CI 0.1, 0.9). CONCLUSIONS: There is no support in our data for the concern that smoking cessation would result in smokers’ increased risk of some mental disorders. To the contrary, our data suggest that smoking cessation is associated with risk reduction for mood/anxiety or alcohol use disorder, even among smokers who have had a pre-existing disorder

Gonococci with mutations to low-level penicillin resistance exhibit increased sensitivity to the oxygen-independent bactericidal activity of human polymorphonuclear leukocyte granule extracts.

Gonococci which cause disseminated gonococcal infection are nearly always highly penicillin sensitive, in contrast to many isolates causing uncomplicated gonorrhea. We questioned whether any of the known chromosomal mutations to low-level penicillin resistance might adversely affect virulence. The penA2 locus is known to result in low-level resistance to penicillins, whereas mtr-2 results in nonspecific resistance to a variety of antimicrobial agents. We found that the penA2 and mtr-2 mutations each markedly increased sensitivity of strain FA19 to oxygen-independent killing by human polymorphonuclear leukocyte mixed or isolated azurophilic granule extracts. The penA2 and mtr-2 mutations had no effect on sensitivity to serum antibody and complement. Isogenic opaque or transparent variants of several strains of Neisseria gonorrhoeae were equally resistant to human polymorphonuclear leukocyte mixed granule extract bactericidal systems. There were also no differences in susceptibility of piliated type 1 and nonpiliated type 4 variants to human polymorphonuclear leukocyte mixed granule extracts. Since the penA2 and mtr-2 loci are known to increase the degree of cross-linking of cell wall peptidoglycan, the structure of peptidoglycan apparently affects sensitivity to killing by one or more polymorphonuclear leukocyte azurophilic granule extract bactericidal systems. These observations might explain why gonococci with mutations similar to penA2 and mtr-2 are almost never isolated from patients with disseminated gonococcal infection