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P G Sohnle

Publications and source records attributed to P G Sohnle.

At least 37 records · Page 2Linked to original sources
PubMed1994

Comparison of the metal-binding anticandidal activities of serum and abscess fluid supernatants.

Serum transferrin appears to play a role in host defense by competing with invading microorganisms for iron. The purpose of the present study was to compare this activity to a similar one recently described in abscess fluids and based on a calcium- and zinc-binding protein called calprotectin. Serum and abscess fluid supernatants were collected and pooled from groups of five to 10 C57BL/6 mice with experimental Candida albicans abscesses; serum was also collected from normal animals. In four experiments, serum was found to reduce in vitro C. albicans growth in Sabouraud glucose broth by a mean of 97.9% at 10 mg ml-1 of protein; this effect was reversed by adding 3-10 microM FeCl3, but not by similar amounts of ZnSO4. Abscess fluid supernatants had a greater effect, reducing growth by 99.9% at 1 mg ml-1 and 76.1% at 0.1 mg ml-1 of total protein; this effect was reversed by 3-10 microM ZnSO4, but not FeCl3. Although abscess fluid supernatants were effective when high inocula (10,000 yeast cells) were used, serum from the infected mice inhibited growth only with lower inocula (10-100 yeast cells). In a separate study, serum from infected mice (eight pools) reduced growth (by a range of 36 to 97%), whereas serum from normal mice (five pools) actually enhanced growth in this system (by a range of 173 to 595%).(ABSTRACT TRUNCATED AT 250 WORDS)

Abscess↗
PubMed1993

Inhibition of pseudohyphal growth as a neutrophil-mediated host defense mechanism against experimental deep Candida albicans infections in mice.

Neutrophils have recently been found to have microbistatic activity in addition to their well-described microbicidal mechanisms; therefore, a murine model of deep candidiasis was used to evaluate the possibility that both antimicrobial activities might participate in the host defense against this type of infection. In nonleukopenic animals, subcutaneous injection of Candida albicans yeast cells produced local abscesses and early metastatic spread of the infection to the kidneys. Although completely isolated within a dense neutrophilic infiltrate, a significant proportion of the fungal cells in the subcutaneous abscesses of these animals remained viable for at least 6 to 10 days after inoculation; the infections at this site were observed to resolve after spontaneous rupture of the abscesses. Growth of the organisms appeared to be suppressed at later time points in these animals, as evidenced by the markedly reduced proportions of multicelled pseudohyphae (representing organisms that had undergone cell division) observed in their abscess exudates as compared with those in samples from leukopenic animals. In addition, at 10 days after inoculation, very few multicelled pseudohyphae were observed histologically in the subcutaneous infections of nonleukopenic animals, whereas masses of these forms were found in leukopenic ones. Fluids from the abscesses of the nonleukopenic animals appeared to contain growth-inhibiting activity for C. albicans, in that the organisms could not grow in them unless additional zinc were to be added to the medium. This type of zinc-reversibility is a characteristic of neutrophil microbistatic activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Abscess↗
PubMed1992

Inefficiency of in vivo candidacidal mechanisms in experimental subcutaneous infections with Candida albicans in mice.

A murine model of subcutaneous Candida albicans infections was used to evaluate host defenses against inocula of from 10(1) to 10(8) yeast cells. In these experiments, small inocula did not produce abscesses that drained to the skin surface, whereas larger ones did. Also, small numbers of organisms often remained at the infected sites for up to 21 days after inoculation with either small or large numbers of organisms. The data from these studies suggest that the in vivo candidacidal mechanisms in these infections are relatively inefficient and that they therefore may require some additional mechanism to control proliferation of the remaining organisms.

Animals↗
PubMed1992

The fate of individual organisms during clearance of experimental cutaneous Candida albicans infections in mice.

A mouse model of acute cutaneous Candida albicans infections was used to study the manner in which these infections are cleared. Results of histological examination were correlated with determinations of the viability by acridine orange staining of superficial C. albicans pseudohyphae retrieved from the surface of the infected skin. The number of organisms retrieved from the skin surface was highest on the third and fourth day after inoculation, a finding which appeared to relate to a loss of Candida foci observed histologically to occur after the second day. Viability was high (approximately 80%) for at least 1-2 days after the organisms were seen histologically to have become associated with neutrophils and extruded from the stratum Malpighi into the stratum corneum; however, at later time points (fourth and fifth day after inoculation), the viability of the retrieved organisms did decline. Pseudohyphae germinated in vitro and applied to the skin of mice were found to be non-viable when retrieved 24 h later. These data suggest that the microbicidal processes of neutrophils may not be required for resolution of these infections. They are most consistent with clearance through an epidermal proliferative response which relocates the infecting organisms to a very superficial site, from which they can be either lost in a viable state, or subjected to killing by other factors at the skin surface.

Acute Disease↗
PubMed1991

Antimicrobial activity of an abundant calcium-binding protein in the cytoplasm of human neutrophils.

Studies of experimental infections in animals indicate that phagocytic cells may sometimes control infective foci without actually ingesting or contacting the invading microorganisms. In the present study, an effective inhibitor of Candida albicans growth, previously detected in neutrophils cytoplasm and found to be released only after lysis of the cells, was identified as an abundant calcium-binding protein originally described in neutrophils as the L1 myelomonocytic antigen or the cystic fibrosis antigen. This substance was demonstrated also to have static activity against several other important human pathogens, including Aspergillus fumigatus, Staphylococcus aureus, and Escherichia coli. Growth of the various microorganisms was inhibited to considerably different degrees by the neutrophil protein, with the effects on S. aureus (the least responsive organism) being significantly enhance by addition of calcium to the medium. These findings suggest that after its release by the death of neutrophils at sites of tissue infection, this abundant calcium-binding protein could have a host defense function by controlling the growth of pathogenic microorganisms that escape being killed initially and would otherwise be free to proliferate.

Aspergillus fumigatus↗
PubMed1991

The zinc-reversible antimicrobial activity of neutrophil lysates and abscess fluid supernatants.

There is some evidence to suggest that microbial growth inhibition may occur in chronic abscesses. A substance perhaps responsible for this phenomenon is calprotectin, a neutrophil cytoplasmic protein that inhibits microbial growth and that belongs to a class of proteins often having specific binding sites for zinc. In the present study, the suppressive effects of either human or mouse neutrophil lysates on Candida albicans growth were found to be completely reversed by micromolar quantities of zinc but not by iron or other trace elements. Similarly, supernatants of exudates from experimental abscesses in mice or from clinical specimens of abscesses in humans markedly inhibited the proliferation of C. albicans, and this effect was also completely reversed by zinc. A protein complex characteristic of calprotectin was identified in the abscess fluids. Preparations of the neutrophil growth-inhibiting protein, containing predominantly calprotectin, were shown to have zinc-binding activity by a dialysis technique. These findings suggest that the major mechanism of C. albicans growth inhibition by abscess fluids is through competition for zinc by a cytoplasmic protein apparently released from dying neutrophils.

Abscess↗
PubMed1990

Comparison of candidacidal and candidastatic activities of human neutrophils.

Disruption of neutrophils causes the release of a cytoplasmic protein which can inhibit the growth of Candida albicans without killing the organisms. The present study was undertaken with a combined system in which candidacidal and candidastatic activities of human neutrophils could be compared. In this system it was found that disruption of either half or all of the neutrophils in the samples markedly improved the ability of the cells to handle an inoculum of Candida yeast cells over a 48-h period, even though the disrupted cells had primarily candidastatic activity, with very little candidacidal activity.

Candida albicans↗
PubMed1990

The effect of chemical modification of quartz surfaces on particulate-induced pulmonary inflammation and fibrosis in the mouse.

One of the critical steps in the development of crystal-induced lung diseases is thought to be the interaction of crystal surfaces with cell membranes. The effect of chemical modifications of the surface of alpha-quartz on the development of lung disease has been investigated by treating quartz with various organosilanes. The functional groups attached to the quartz surfaces were (-CN), (-CH3), (-NH2), and -(N(CH3)3+). After intratracheal injection of each modified crystal at a constant surface area into mice, pulmonary inflammation and fibrosis were assessed 6 wk postexposure to the crystals by lung wet weight (lung index) and by the level of hydroxyproline in the lung. The crystals showing the highest degree of biologic activity were native quartz, which has a negative charge, -N(CH3)3+ modified quartz, which has a positive charge, and -CN modified quartz, which has no charge. One of the crystals with chemical groups capable of hydrogen bonding, the -NH2 modified quartz, was as unreactive as the crystal preparation modified with a hydrophobic group, -CH3. If the -CH3 and -NH2 modified quartz are compared as a less reactive group with the more reactive native quartz and -N(CH3)3+ modified quartz, these experiments suggest that electrostatic interactions may be more important in determining effective biologic activities than are hydrogen bonding interactions.

Animals↗
PubMed1989

Epidermal proliferation and the neutrophilic infiltrates of experimental cutaneous candidiasis in mice.

A mouse model of cutaneous candidiasis was used to determine if the prominent neutrophilic infiltrates in the infected skin of nonimmune animals were responsible for inducing the early phase of epidermal proliferation seen in these infections. Both the organisms and resulting neutrophilic microabscesses were found in the cellular layers of the epidermis at 12 h after inoculation, and were then extruded together to a more superficial site in the stratum corneum over the next 1-2 days. The degree of epidermal proliferation elicited at the site of the Candida foci, as determined from the thickness of the cellular layers of the epidermis, was the same for foci with neutrophils as for those without, even when the latter came from severely leukopenic animals. The location of neutrophils within the infected skin or the numbers of organisms present did not seem to make a difference with respect to the degree of epidermal proliferation produced at the site of Candida foci. These data suggest that in acute experimental cutaneous Candida infections the organisms can elicit a vigorous epidermal proliferative response in the absence of the neutrophilic infiltrates usually seen in these infections.

Animals↗
PubMed1989

Effect of particle size on quartz-induced hemolysis and on lung inflammation and fibrosis.

To assess the role of crystal size in biologic responses, we quantitated red blood cell lysis and lung inflammation and fibrosis in the mouse using 4 alpha-quartz preparations with average diameters of 1, 5, 7.8, and 11.2 microns. When compared on the basis of identical crystal surface areas, the 1-micron fraction was more hemolytic than the other 3 fractions. The three larger fractions had equivalent membranolytic activities. After 6 weeks of postintratracheal instillation of the crystals into mice, the 1-micron-diameter crystal fraction increased wet lung weights by 1.25 x that of saline controls, while a 1.75 x increase was found for the three larger crystal fractions. A similar response was found when evaluating fibrosis development by determining lung hydroxyproline levels. Measurement of the percentage of the crystal dose remaining in the lungs revealed that the biologic differences observed were not due to a difference in the clearance of the smaller crystal fraction. Thus, larger crystals of alpha-quartz produce a greater degree of inflammation and fibrosis when instilled into the lung than those of 1 micron diameter, even though the smaller crystals are more membranolytic in vitro and appear to be cleared from the lung at the same rate as the larger crystals.

Animals↗
PubMed1989

Candidacidal activity of the neutrophil myeloperoxidase system can be protected from excess hydrogen peroxide by the presence of ammonium ion.

Excessive concentrations of hydrogen peroxide inhibit the neutrophil myeloperoxidase system, presumably by inactivating the hypochlorous acid produced by this system. Ammonium ion generated by neutrophils and other cells can react with hypochlorous acid to produce monochloramine, an oxidant with good microbicidal activity, but relative resistance to inactivation by other compounds. In an assay based on the oxidation of 5-thio-2-nitrobenzoic acid, hydrogen peroxide reacted more readily with sodium hypochlorite (used as a source of hypochlorous acid) than with monochloramine. Also, in this assay Candida albicans yeast inactivated the oxidant activity of hypochlorous acid more completely than they did that of monochloramine. The killing of Candida by sodium hypochlorite, as determined in a standard colony count microbicidal assay, was inhibited by equimolar and greater concentrations of hydrogen peroxide; killing of this organism by monochloramine was not affected by a tenfold excess concentration of hydrogen peroxide. In microbicidal assays using 4 mU of myeloperoxidase and optimal or excessive concentrations of hydrogen peroxide or glucose and glucose oxidase to generate hydrogen peroxide, the excessive concentrations inhibited killing of Candida, but not Staphylococcus aureus. The inhibition of Candida killing could be reversed by addition of ammonium ion to convert hypochlorous acid to monochloramine. These results indicate that for certain organisms such as C albicans, conversion of hypochlorous acid to monochloramine by reactions with ammonium ion may extend the range of hydrogen peroxide concentrations under which killing by the myeloperoxidase system can occur by protecting the necessary microbicidal oxidants from inactivation by excess hydrogen peroxide.

Ammonia↗
PubMed1989

Effect of immunosuppression on epidermal defenses in a murine model of cutaneous candidiasis.

A number of pharmacologic treatment regimens were used to evaluate the early defenses against experimental cutaneous candidiasis in nonimmune mice. Severe immunosuppression of the animals was found to have little effect on the numbers of Candida pseudohyphae that initially infected the skin, but it did, however, modify the progression of the infection afterwards. Of the regimens tested, only the combination of intraperitoneal cyclophosphamide and intravenous phorbol myristate acetate both completely eliminated the epidermal neutrophilic infiltrates characteristic of these infections and promoted a significant degree of Candida invasion into the dermis. However, the epidermal proliferative response to the infections, generally considered to be an important mechanism of defense against superficial mycoses, was equivalent at the sites of both invasive and noninvasive foci, and it was generally comparable to that in normal animals. Dermal invasion in the treated animals was also found to occur at a time (between 12 and 24 hours after inoculation) when the epidermis was maximally proliferating. In contrast to these results, the intraperitoneal administration of colchicine significantly suppressed epidermal proliferation at the Candida foci but had only minimal effects in promoting dermal invasion. Therefore, whereas epidermal proliferation could be involved in the eventual clearance of these experimental cutaneous Candida infections, this mechanism apparently has little to do with either limiting the number of organisms initially infecting the skin or preventing their invasion into the dermis.

Animals↗
PubMed1988

Neutrophil death as a defence mechanism against Candida albicans infections.

In studies of experimental Candida albicans infections, growth of invading organisms sometimes ceased before the organisms reached the neutrophil infiltrates. Lysates of human neutrophils inhibited the directed growth of candida pseudohyphae in agarose gel and suppressed the proliferation of candida yeast in broth cultures, but did not kill the organisms or prevent their germination. The growth-inhibitory material released from disrupted neutrophils had an estimated molecular weight of 30 kD and differed from most previously described neutrophil antimicrobial factors in that it was present in cell sap rather than granules, and did not appear in the supernatant after stimulation of the cells. Neutrophil death and dissolution may represent an alternative host defence mechanism against invasive C albicans infection.

Animals↗
PubMed1988

Neutrophil accumulation and cutaneous responses in experimental cutaneous candidiasis of genetically complement-deficient mice.

Mice deficient in the fifth component of complement were studied for their ability to respond to and clear experimental cutaneous Candida albicans infections. The complement-deficient animals took longer to clear the infections and developed a significantly greater delayed hypersensitivity response to Candida than did normal animals. However, although the serum of the complement-deficient animals was incapable of generating in vitro chemotactic activity for neutrophils after appropriate stimulation, the epidermal neutrophilic infiltrate in the Candida-infected skin of these animals was equivalent to that in the normal animals. The progression of the infection, including the early relocation of the invading Candida pseudohyphae to a more superficial site in the stratum corneum and the thickening of the epidermis itself, was also similar in the complement-deficient and normal animals. Therefore, although mice lacking the fifth complement component cannot generate complement-derived serum chemotactic factors and are somewhat less efficient in clearing experimental cutaneous candidiasis, the accumulation of neutrophils in the Candida-infected skin of these animals and their initial cutaneous responses to the infections are normal.

Abscess↗
PubMed1988

Characteristics of dermal invasion in experimental cutaneous candidiasis of leucopenic mice.

The course of experimental cutaneous Candida albicans infections produced in mice made leucopenic by the administration of cyclophosphamide was compared to that in untreated animals. In the latter, neutrophils characteristically infiltrated the area of infection and the organisms were virtually always confined to the epidermis. However, even though many fewer foci of infection were associated with neutrophils in the cyclophosphamide-treated animals, a majority of these foci were also unable to penetrate past the epidermis. Although Candida yeast proliferated relatively poorly when cultured in homogenates of skin lacking the epidermis, Candida pseudohyphae could invade into the dermis if inoculated skin was isolated from normal animals and cultured in vitro, or if the epidermis was removed by gentle scraping prior to inoculation with Candida yeast onto the remaining skin of leucopenic animals. Therefore, in the absence of neutrophil contact and killing of Candida pseudohyphae in the epidermis, other cutaneous defense mechanisms appear to be capable of preventing invasion of a majority of the organisms into the dermis. These findings may help to explain why deep Candida infections are rare in patients who have extensive superficial candidiasis.

Animals↗
PubMed1988

The effect of crystal structure on mouse lung inflammation and fibrosis.

In order to identify the physical and structural parameters that relate best to the membranolytic, inflammatory, and fibrotic potentials of different silicon dioxide (SiO2) and titanium dioxide (TiO2) crystals, we have studied the potential of four different SiO2 and two different TiO2 crystal structures to lyse human red blood cells and to induce pulmonary inflammation and fibrosis in mice. The crystals studied were quartz, tridymite, cristobalite, coesite, anatase, and rutile. Mice were injected intratracheally with each crystal at constant surface area. Inflammation and fibrosis were assessed 6 wk after crystal instillation by wet lung weight (lung index), protein concentration of lung lavage fluid, the level of hydroxyproline in the lung, and histologic examination. In vitro red blood cell (RBC) lysis was evaluated by incubating the crystals with 51Cr-labeled RBC and measuring the release of 51Cr into the medium. Known crystallographic data for each of the minerals were used to calculate the percent occupied volume. Biologic activity seemed to correlate with percent occupied volume, suggesting that surface molecular topology may be important in crystal-cell interactions. The crystals with more irregular surfaces and protruding oxygen atoms, which form surface pockets (quartz, tridymite, and cristobalite), showed a dramatic increase over saline controls for lung index (greater than 2 x), cell number and lavage protein concentration (greater than 4 x), and hydroxyproline level (greater than 2 x). The other more boxlike crystals (coesite, anatase, and rutile) displayed little change in these parameters.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗