Effect of carbon tetrachloride on hamster tracheal epithelial cells.

This study was designed to assess effects of carbon tetrachloride (CCl4) in hamster tracheal epithelium. Adult, male, Syrian golden hamsters were treated with 2.5 ml/kg CCl4 ip, and controls received only the vehicle (peanut oil). Animals were sacrificed after 1, 4, 12, and 24 h. Tissue samples from upper and lower tracheal levels were fixed and embedded in glycol methacrylate for light microscopy. Some tracheal rings were also fixed in formaldehyde/glutaraldehyde cacodylate buffer for transmission electron microscopy. For histopathologic evaluation of the tracheal epithelial cells, each tracheal level was cut transversely at 3 microns and stained with toluidine blue. CCl4 produced injury to ciliated and nonciliated cells in all portions of hamster trachea, although the severity of CCl4-induced injury differed in various levels and regions. The number of damaged cells increased markedly after 1 h in the lower trachea, but not until after 4 h in the upper trachea. By 24 h, the number of injured cells had decreased so that no significant difference from control was evident. The ultrastructural alterations in epithelial cells were obvious as early as 1 h after CCl4 administration. Intracellular organelles, including smooth and rough endoplasmic reticulum, mitochondria, and Golgi apparatuses, were damaged by this chemical. Since CCl4-induced cell injury is dependent on metabolism by intracellular NADPH-dependent cytochrome P450 monooxygenases, these results suggest that hamster tracheal epithelial cells have the potential to activate CCl4 metabolically.

Haemorrhagic endovasculitis of the placenta: a review with clinical correlation.

Haemorrhagic endovasculitis (HEV) is a recently described vasodestructive process within the placenta. Similarities to several forms of thrombotic microangiopathy are evident. Clinical studies have shown strong associations between HEV, still birth and intrauterine growth retardation (IUGR). Liveborn infants, with affected placentae, evaluated at the age of five, exhibit a high incidence of neurological abnormalities. HEV has been recurrent in successive pregnancies in some patients. Clinicopathological processes, which appear to be associated with HEV, include the presence of chronic villitis (VUA) and maternal hypertension. Viral- and/or Mycoplasma-type particles have been identified in a number of affected placentae examined by electron microscopy. Associated pathological events suggest an infectious aetiology possibly acting in concert with an environmental toxin. Biochemical factors and alterations of immune response within the maternal-placental-fetal unit may be involved.

Effect of polybrominated biphenyls, beta-naphthoflavone and phenobarbital on arylhydrocarbon hydroxylase activities and chloroform-induced nephrotoxicity and hepatotoxicity in male C57BL/6J and DBA/2J mice.

Administration of chloroform (CHCl3) to male C57/6J (C57) and DBA/2J (DBA) mice produced dose-dependent hepatic and renal damage. Hepatic arylhydrocarbon hydroxylase (AHH) activity was higher in C57 than DBA mice; in kidney, AHH activity was higher in DBA than in C57 mice. CHCl3 caused the same degree of liver damage in both strains of mice; however, nephrotoxicity of CHCl3 was greater in DBA than in C57 mice. Pretreatment of C57 and DBA mice with phenobarbital (PB) markedly increased hepatic AHH activity and hepatotoxicity of CHCl3 in both strains but did not affect renal AHH or nephrotoxicity of CHCl3. Similarly, beta-naphthoflavone (BNF) enhanced AHH activity and CHCl3 hepatotoxicity in C57 mice, but had little effect on nephrotoxicity. BNF did not affect hepatic AHH nor CHCl3-induced hepatic injury in male DBA mice. Pretreatment with polybrominated biphenyl (PBB) enhanced AHH activity in liver and CHCl3 hepatotoxicity in both strains. After PBB, nephrotoxicity of CHCl3 and renal AHH activity were increased in C57 mice whereas PBB did not alter nephrotoxicity or renal AHH in DBA mice. These results suggest that CHCl3-nephrotoxicity is independent of hepatotoxicity.

Morphologic and cytochemical characteristics of amine-containing globule leukocytes in rat tracheal epithelium.

Amine-containing cells in the tracheal epithelium are typically of the small-granule type (diameter approximately 100 nm). However, in the rat, another amine-containing cell type has been identified that possesses the amine-handling features of the APUD-series of cells (amine precursor uptake and decarboxylation) but not the ultrastructural characteristics. It has been postulated that these cells may be related to cutaneous melanocytes. In this study, fluorescent cells were present in the laryngeal and tracheal epithelial lining of adult Sprague-Dawley rats following freeze-drying and exposure to formaldehyde vapor (FIF or formaldehyde-induced fluorescence). Microspectrofluorimetry revealed an emission maximum at 493 nm. The excitation maximum could not be calculated but appeared to be around or below 350 nm (to record spectra below requires the use of quartz optics). Yellow fluorescence also emanated from serotonin-containing mast cells (excitation and emission maxima: 401/515 nm). Tracheal segments processed according to the aqueous formaldehyde ( AFIF ) technique, for the demonstration of 5- hydroxytryptophan (5-HTP) or serotonin (5-HT), failed to identify fluorescent cells in the epithelial lining even though connective-tissue mast cells were evident. Subsequent treatment of AFIF -fixed sections with formaldehyde and HCl vapors ( AFIF -HCl) resulted in the formation of a fluorogenic compound within numerous cells in the tracheal lining (455/537 nm). This spectral shift and increase in intensity of fluorescence following acidification are characteristic for standards and/or cells that contain tryptamine, tryptophan, or peptides with NH2-terminal tryptophan and are markedly different from microspectrofluorimetric data reported for the phenylethylamines or serotonin. It is therefore postulated that these cells contain a closely related beta-(3-indolyl) ethylamine-like compound, serotonin excluded. The morphology of the fluorescent cells was similar when prepared according to the FIF or AFIF -HCl techniques. Conjunctive staining, the examination of a single section first by fluorescence microscopy and subsequently by other histochemical and cytochemical methods, demonstrated that the fluorescent granules were also methylene blue, alcian blue, periodic-acid Schiff, and ferric- fericyanide positive. Subsequent correlative electron microscopic examination of Epon-embedded AFIF -HCl-treated tracheal sections demonstrated that these amine-containing cells were globule leukocytes.

Sex and strain differences in mouse kidney: Bowman's capsule morphology and susceptibility to chloroform.

Chloroform (CHCl3) produces liver damage in male and female mice but renal injury only in male mice. Previous reports demonstrated that the parietal epithelium of Bowman's capsule in female mice is composed of squamous cells, whereas the parietal cells of Bowman's capsule from male mice consist of a mixture of squamous and cuboidal cells or purely cuboidal cells. These data suggested that the factor(s) associated with these histological differences may similarly be associated with factors that determine susceptibility to tubular damage from chloroform. The susceptibility of male mice to chloroform nephrotoxicity varies with animal strain. In the present study, administration of CHCl3 to male C57BL/6J (C57) and male and female DBA/2J (DBA) mice produced dose-dependent kidney tubular damage in male C57 and male DBA mice. However, CHCl3 nephrotoxicity was considerably greater in male DBA mice than in male C57 mice. Female DBA mice failed to develop renal damage following administration of CHCl3. Male DBA mice had a higher percentage of cuboidal parietal epithelial cells in Bowman's capsule whereas male C57 mice had a higher percentage of squamous cells in the parietal epithelium. The parietal epithelium in Bowman's capsule of female DBA mice was predominantly squamous. Since morphological differences between sex and strain of mice occurred in the capsular epithelium, and the differences in susceptibility to CHCl3 appear to be a tubular phenomenon, it is unlikely that there is a causal relationship between the structure of Bowman's capsule and chloroform-induced renal tubular necrosis; rather, these two independent phenomena are regulated by some common factor(s), possibly testosterone.

The effects of carbon monoxide and hypoxic hypoxia on amine-containing cells in the tracheal epithelium of young rabbits.

Endogenously fluorescent, singly occurring amine-containing cells in tracheal epithelium were examined in 3-, 10-, and 28-day-old rabbits. These cells are pyramidal in shape with the apex projected toward the tracheal lumen. The cytoplasm exhibits a yellow fluorescence which is predominantly supranuclear. Occasional, infranuclear, fluorescent cytoplasmic processes project from the cells. The numbers of fluorescent cells per unit length of trachea increase with age. Acute exposure of 10-day-old rabbits to 13% O2 decreases the number of detectable fluorescent cells in the tracheal compared to controls exposed to room air. Similarly, exposure to 750 ppm carbon monoxide decreases the number of fluorescent epithelial cells appearing in tracheas of 10- and 28-day-old rabbits. These results suggest that the amine-containing epithelial cells of the trachea respond to tissue hypoxia and that decreased airway pO2 is not necessary to elicit a response.

Morphology, histochemistry, and distribution of serotonin-containing cells in tracheal epithelium of adult rabbit.

We have investigated morphologic and histochemical characteristics of serotonin-containing epithelial cells in tracheas from adult rabbits, using the Falck-Hillarp freeze-dried formaldehyde vapor technique. An intracellular formaldehyde-induced fluorescent substance was identified as serotonin by microspectrofluorometric techniques. Fluorescence microscopy and subsequent histochemical staining of the same sections demonstrated that serotonin-containing cells were argentaffin-, argyrophil-, and ferric ferricyanide-positive. The serotonin-containing epithelial cells were more numerous in ventral than in dorsal aspects of trachea. The number of detectable fluorescent cells was reduced after reserpine administration but was not affected by injecting the amine precursor L-dihydroxyphenylalanine (L-DOPA). The emission peak of the fluorophore was not significantly shifted after L-DOPA injections. The cells may regulate tracheobronchial-pulmonary function by releasing serotonin or other as yet unidentified biologically active substances.