Independence of neutrophil respiratory burst oxidant generation from the early cytosolic calcium response after stimulation with unopsonized Candida albicans hyphae.

We previously noted differences between neutrophil responses to unopsonized Candida albicans hyphae and responses to other particulate stimuli such as opsonized hyphae or zymosan; these differences include delayed rises in cytosolic calcium [( Ca2+]i), 1,4,5-inositol trisphosphate, and superoxide release and the total absence of early membrane depolarization. Respiratory burst stimulation is required for killing of C. albicans hyphae.

Natural inhibitor from Candida albicans blocks release of azurophil and specific granule contents by chemotactic peptide-stimulated human neutrophils.

A product released by Candida albicans hyphae which was previously determined to block the neutrophil respiratory burst also inhibited the degranulation response elicited by the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP). When neutrophils were incubated with 100 micrograms of this Candida hyphal inhibitory product (CHIP) per ml and stimulated with 1,000 nM FMLP, release of the azurophil granule marker beta-glucuronidase and the specific granule marker lactoferrin was decreased to 31.2 +/- 5.

Induction of signal transduction in human neutrophils by Candida albicans hyphae: the role of pertussis toxin-sensitive guanosine triphosphate-binding proteins.

Nonopsonized Candida hyphae elicit from human neutrophils a transient rise in cytosolic calcium concentrations and an oxidative burst without a detectable change in membrane potential. To determine if the signal-transduction pathway used by these organisms is mediated by guanine nucleotide-binding proteins (GNPs), we examined the functional responsiveness of neutrophils pretreated with pertussis toxin (PT). In response to serum-opsonized hyphae or zymosan, the rise in cytosolic calcium, membrane depolarization, and the respiratory burst were only partially abrogated.

Stimulation of neutrophil actin polymerization and degranulation by opsonized and unopsonized Candida albicans hyphae and zymosan.

We previously showed that unopsonized Candida albicans hyphae stimulated a delayed rise in the putative neutrophil second messengers Ca2+ and inositol 1,4,5-trisphosphate and subsequent O2- release, as compared with opsonized hyphae or zymosan. Therefore, cytoskeletal and degranulation temporal responses to these stimuli were examined. Unopsonized zymosan elicited no neutrophil responses under the experimental condition used.

Fungal surfaces: effects of interactions with phagocytic cells.

Fungal surfaces undergo profound changes during morphogenesis that modify host responses. For example, inhaled spores or conidia of Rhizopus or Aspergillus lose their surface hydrophobic outer layers, initially swell, and then germinate to form mycelia that may invade tissues. These various fungal forms not only elicit differing response from host phagocytic cells but also differ in their susceptibilities to cellular microbicidal mechanisms.

Histatins, a novel family of histidine-rich proteins in human parotid secretion. Isolation, characterization, primary structure, and fungistatic effects on Candida albicans.

Histatins 1, 3, and 5 from human parotid secretion were isolated by gel filtration on Bio-Gel P-2 and reverse phase high performance liquid chromatography. The complete amino acid sequences of histatins determined by automated Edman degradation of the proteins, Staphylococcus aureus V8 protease, and tryptic peptides, are as follows: (Sequence: see text). Histatins 1, 3, and 5 contain 38, 32, and 24 amino acid residues, have molecular weights of 4929, 4063, and 3037, respectively, and contain 7 residues of histidine.

A novel natural inhibitor from Candida albicans hyphae causing dissociation of the neutrophil respiratory burst response to chemotactic peptides from other post-activation events.

Previous work established that Candida albicans hyphae release several inhibitors of human neutrophil function. We now report that the crude hyphal inhibitory product (CHIP) inhibits superoxide anion (O2-) production stimulated by FMLP in a dose-related manner with an EC50 of approximately 2 micrograms/ml. CHIP also inhibited O2- production stimulated by A23187 and by opsonized zymosan, although this effect could be overcome by increasing the concentration of agonist.

Synchronous bacterial and fungal septicemia. A marker for the critically ill surgical patient.

Mixed septicemia (synchronous fungal and bacterial septicemia) is an occasional, but often fatal occurrence in the critically ill patient. We reviewed 14 such cases at two hospitals. Twelve of 14 patients were in the surgical intensive care unit.

Temporal association of calcium mobilization, inositol trisphosphate generation, and superoxide anion release by human neutrophils activated by serum opsonized and nonopsonized particulate stimuli.

We have investigated the involvement of phospholipase C mediated polyphosphoinositide turnover in activation of polymorphonuclear leukocytes by particulate stimuli. Results showed that stimulation of leukocytes with serum opsonized zymosan (ingestible particle), serum opsonized Candida albicans hyphae (noningestible particle), or nonopsonized hyphae was followed by a transient rise in cellular inositol phosphates as has been described for neutrophil activation via the formyl peptide receptor. The kinetics of inositol trisphosphate generation paralleled both the time course of changes in cytosolic calcium concentration and the onset of superoxide anion generation, suggesting that these may be related events.

A model community psychiatry curriculum for psychiatric residents.

The ability of mental health practitioners to work well with persons with serious long-term mental illness has expanded significantly over the past two decades. Learning to do this well involves acquiring a broad base of knowledge and a complex range of skills. Such knowledge and experience must be incorporated into the basic residency curriculum for general psychiatrists, though with some notable exceptions this has not occurred for a number of important reasons, including money and the new image that psychiatry is trying to assume.

Cytosolic calcium changes in individual neutrophils stimulated by opsonized and unopsonized Candida albicans hyphae.

Previous experiments suggest the critical central role of the neutrophil (PMN) respiratory burst in the prevention and containment of disseminated candidiasis. A rise in cytosolic free calcium concentrations ([Ca2+]i) has been documented as an early event after PMN stimulation which is involved in the subsequent genesis of microbicidal and inflammatory respiratory burst products. [Ca2+]i were therefore determined in individual PMN, loaded with the fluorescent calcium probe fura-2 as they attached to and spread over serum-opsonized or unopsonized Candida albicans hyphae, particles that are too big to be completely ingested.

Unopsonized Candida albicans hyphae stimulate a neutrophil respiratory burst and a cytosolic calcium flux without membrane depolarization.

We have defined major differences between events elicited during activation of human neutrophils by opsonized Candida hyphae (noningestible) or zymosan (ingestible) and by unopsonized Candida hyphae (also noningestible). In response to opsonized particles, a transient increase in cytosolic free calcium was initially observed, followed by depolarization in the transmembrane potential and a respiratory burst. Without opsonins, zymosan did not elicit a response from neutrophils.