Acquired resistance to the human hookworm Necator americanus in mice

BALB/c mice were exposed to primary or secondary infection with the hamster-adapted strain of Necator americanus, and the course of infection was monitored through worm recovery and immunological assays. Significantly fewer viable larvae were recovered from the skin site of reinfected mice on day 2 post-infection, and fewer larvae resided in the lungs of challenged mice 3-5 days after infection, suggesting that the skin was involved in resistance to secondary infection. The serum antibody response to L3 antigen was enhanced during secondary infection, peaking on day 9, and the bronchoalveolar leucocyte (BAL) response was more intense at this stage. Thus the secondary BAL response was initiated more promptly than the primary response, peaking on day 13 at twice the intensity of the primary response and five times above the resting level. Differential counts revealed that by far the most significant changes in cell populations were those observed for eosinophils in lavage fluid. At the peak of the response a 925-fold increase over control levels was detected in mice undergoing a challenge infection. Some cellular and serological components of the secondary response were defined in the present work and it was concluded that reinfected mice have the capacity to trap parasites during their passage through the skin and development in the lungs.     

Prekallikrein inhibits innate immune signaling in the lung and impairs host defense during pneumosepsis in mice

Prekallikrein (PKK, also known as Fletcher factor and encoded by the gene KLKB1 in humans) is a component of the contact system. Activation of the contact system has been implicated in lethality in fulminant sepsis models. Pneumonia is the most frequent cause of sepsis. We sought to determine the role of PKK in host defense during pneumosepsis. To this end, mice were infected with the common human pathogen Klebsiella pneumoniae via the airways, causing an initially localized infection of the lungs with subsequent bacterial dissemination and sepsis. Mice were treated with a selective PKK-directed antisense oligonucleotide (ASO) or a scrambled control ASO for 3 weeks prior to infection. Host response readouts were determined at 12 or 36 h post-infection, including genome-wide messenger RNA profiling of lungs, or mice were followed for survival. PKK ASO treatment inhibited constitutive hepatic Klkb1 mRNA expression by >80% and almost completely abolished plasma PKK activity. Klkb1 mRNA could not be detected in lungs. Pneumonia was associated with a progressive decline in PKK expression in mice treated with control ASO. PKK ASO administration was associated with a delayed mortality, reduced bacterial burdens, and diminished distant organ injury. While PKK depletion did not influence lung pathology or neutrophil recruitment, it was associated with an upregulation of multiple innate immune signaling pathways in the lungs already prior to infection. Activation of the contact system could not be detected, either during infection in vivo or at the surface of Klebsiella in vitro. These data suggest that circulating PKK confines pro-inflammatory signaling in the lung by a mechanism that does not involve contact system activation, which in the case of respiratory tract infection may impede early protective innate immunity. © 2019 Authors. Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.     

Xenografted human whole embryonic and fetal entoblastic organs develop and become functional adult-like micro-organs.

BACKGROUND AND AIMS: The aim of this study was to study the morphological and functional development in vivo of whole human embryonic and fetal stomachs, intestines, tracheas, and lungs, which would otherwise be ethically and technically impossible to perform in utero, by microsurgically grafting these organs into nude mice. MATERIALS AND METHODS: Five hundred fifty-seven human organs obtained from legally aborted embryos and fetuses of 6-10 weeks were microsurgically grafted into nude mice for 1 to 273 days. Following different grafting times, biopsies were taken for optical and electron microscopy, in situ hybridization, and cellular kinetics studies. A catheter was introduced into the human organs in order to collect and analyze secretions. RESULTS: All of the grafts took successfully. Macroscopic growth was fast during the first 6 to 10 weeks, following which organ size was stable. In situ hybridization studies detected only a minute level of mouse mesenchymal chimerism in the grafts. The different epithelial cells differentiated, became of adult type, and remained normal during the remainder of the grafting periods. The pH of gastric juice from stomachs grafted for 10 to over 90 days dropped from 8.0 +/- 0.1 to 1.58 +/- 0.29 over this time period (P < 0.001), intrinsic factor levels were stable, and pepsin ranged from 6.8 +/- 7.8 to 134 +/- 51 units (P < 0.001). CONCLUSIONS: These results demonstrate that the development of entoblastic organs from human embryos and fetuses microsurgically grafted into nude mice is similar to that occurring in utero. As such, this method provides a model for the analysis of whole human organs in development and later normal adult-like micro-organs for physiological, therapeutic, and pathological studies.     

Cholecystokinin octapeptide inhibits the in vitro expression of CD14 in rat pulmonary interstitial macrophages induced by lipopolysaccharide

Obejective To study the effect of cholecystokinin octapeptide (CCK-8) on lipopolysaccharide (LPS)-stimulated pulmonary interstitial macrophages （PIM） in vitroMethods PIM were isolated and cultured in the presence or absence of LPS, CCK-8, proglumide (the antagonist of CCK receptors) and vehicle. The expression of membrane CD14 (mCD14) protein was assayed by flow cytometry and soluble CD14 (sCD14) in the supernatant was analyzed semi-quantitatively by Western blot. TNF-α in the supernatant was detected with ELISA.Results CCK-8, at concentrations of 10［-7］ mol/L and 10［-6］ mol/L, significantly inhibited the expression of mCD14. Release of sCD14 and TNF-α in the supernatant was up-regulated by LPS (1μg/ml) but reduced by CCK-8. The effect of CCK-8 was inhibited by proglumide.Conclusion CCK-8 negatively modulated several functions of LPS-stimulated PIM through CCK receptors. This may be one of the mechanisms for CCK-8 to alleviate inflammation in lung tissue during endotoxemia.     

解毒疏络法预防放射性肺损伤的实验研究

[目的]探讨解毒疏络法防治放射性肺损伤的效果。[方法]雌性SD大鼠随机分为正常组、单纯照射组和防治组。防治组于照射前1周使用解毒疏络药物灌胃,对照组灌服等量生理盐水。直线加速器全胸部照射,照射后5、15、30、60 d处死,取肺组织做病理检查、透射电镜、图像定量分析。[结果]照射后30及60 d肺炎加重(P<0.05),胶原纤维明显增多,肥大细胞增多。电镜显示Ⅱ型细胞线粒体、毛细血管内皮细胞肿胀,防治组炎症减轻(P<0.05),胶原纤维、肥大细胞减少,Ⅱ型细胞线粒体、内皮细胞损伤明显好转。[结论]解毒疏络法能减轻放射性肺损伤炎症反应,减少胶原纤维增殖,有效预防放射性肺损伤。     

The compromised intra-uterine environment: implications for future lung health

1. Epidemiological studies of infants, children and adults indicate that prenatal compromises that restrict fetal growth and cause low birthweight increase the risk of respiratory deficiencies after birth. 2. It is apparent that the lung has a limited ability to recover from early developmental compromises and that altered development can permanently impair lung architecture. 3. Lung development in utero can be adversely affected by factors associated with fetal growth restriction, namely fetal hypoxaemia, reduced substrate supply and hypercortisolaemia. 4. We have conducted a series of studies of respiratory development in chronically catheterized ovine fetuses and postnatal lambs in which growth restriction was induced during late gestation by embolizing the umbilico-placental vascular bed, a technique that replicates key aspects of human placental insufficiency. 5. During late gestation, restricting the growth of the ovine fetus did not alter lung weight or lung liquid secretion or volume when each factor was related to bodyweight, but it did lead to increased lung DNA concentrations and an increased thickness of the air-blood barrier. Expression of pulmonary surfactant proteins A, B and C were not altered and, hence, it was unlikely that surfactant protein synthesis had been impaired by growth restriction. 6. When growth restriction continued to term, lambs were born with a low birthweight and remained small compared with controls for 8 weeks after birth. Low-birthweight lambs were mildy hypoxaemic and compliances of their lungs and chest wall were, respectively, decreased and increased relative to controls. Pulmonary surfactant proteins A, B and C were not deficient, indicating that decreased lung compliance most likely had a structural basis.     

Study of mutagenic activity of dioxidine by the polyorgan micronuclear method

Antibacterial preparation dioxidine administered four times in doses of 10, 100, and 300 mg/kg increased the incidence of micronucleated cells in the bone marrow, lungs, and large intestine of mice. Bone marrow cells were most sensitive, while cells of the lungs and large intestine exhibited lower sensitivity to the cytogenetic effect of dioxidine. Translated fromByulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 138, No. 8, pp. 188–190, August, 2004     

Short rib polydactyly syndrome—type I

Short rib polydactyly syndrome (SRPS) consists of a group of lethal skeletal dysplasias presenting with short limbs and ribs, hypoplastic thorax and polydactyly with or without visceral abnormalities. The authors report a case of SRPS in a fresh stillborn baby who had these features along with dysplastic kidneys. Clinical and radiological findings in this baby were consistent with SRPS-Type I (Saldino-Noonan Type). The diagnosis of SRPS, as in this case, can be made by antenatal ultrasonography     

Viability of mycobacteria in formalin-fixed lungs

It is generally accepted that the risk of contracting tuberculosis is relatively high among medical laboratory workers and pathologists. Nevertheless, there is an assumption that once tissue is fixed in formalin, the risk for transmission and subsequent infection of mycobacteria is greatly reduced, if not altogether eliminated. To test the viability of potentially infectious mycobacteria in formalin-fixed tissue, tissue specimens from autopsy lungs fixed in formalin were cultured for mycobacteria. Of 138 cases with histologic evidence of acid-fast bacilli, 12 grew mycobacteria, including 3 Mycobacterium tuberculosis isolates, suggesting that there is a risk of contracting tuberculosis from tissue that has been fixed in formalin, if aerosolization or accidental inoculation should occur.