Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The production of interleukin 1 (IL 1) by adherent peripheral blood mononuclear cells (PBMC) was quantitated in 16 individuals infected with Histoplasma capsulatum or Blastomyces dermatitidis and 16 age-matched controls. In parallel, we measured blastogenic responses to phytohemagglutinin (PHA) by PBMC from patients and controls. Of the 16 patients, six had pulmonary histoplasmosis, six had disseminated histoplasmosis, two had pulmonary blastomycosis, and two had disseminated blastomycosis. At the time of study, none of the patients were receiving immunosuppressive agents or had an underlying debilitating illness. Proliferative responses by PBMC from patients to PHA were significantly (P less than 0.05) less than the mean response by PBMC from an equal number of controls. In the 16 controls, the increase in secretion of IL 1 by lipopolysaccharide (LPS)-stimulated adherent cells over unstimulated cells ranged from 18 to 40 units of IL 1 activity per 10(5) adherent cells. The increment in IL 1 levels between LPS-stimulated adherent PBMC and unstimulated cells was diminished (less than 18 units of IL 1 activity per 10(5) adherent cells) in five of the 16 patients. Diminished IL 1 secretion in response to LPS was associated with impaired PHA responses in four of 10 patients.
 ...
PMID:Correlative studies of blastogenic responses and interleukin 1 production by mononuclear cells from patients with zoopathogenic fungal infections. 278 78

Cell-mediated immunity is critical in host resistance against the pathogenic fungus Histoplasma capsulatum. To explore the role of L3T4+ T cells in protection of mice against H. capsulatum infection, we examined the effect of in vivo treatment with anti-L3T4 monoclonal antibody (MAb) GK1.5 on the course of murine disseminated histoplasmosis. Treatment with anti-L3T4 antibody caused a profound and selective depletion of L3T4+ T cells that was associated with a significant increase in the number of H. capsulatum CFU recovered from the spleens of mice infected for 1 week. In addition, none of the infected mice treated with MAb GK1.5 survived a sublethal challenge with H. capsulatum yeasts. Histopathological examination of spleens from mice infected for 1 week revealed the presence of granulomatous inflammation in mice depleted of L3T4+ T cells and in infected controls. However, silver stains demonstrated that spleens of infected mice given MAb GK1.5 contained a greater number of yeasts than did spleens from infected controls. MAb GK1.5 did not cause reactivation of infection when administered for 2 weeks beginning 4 weeks after inoculation of Histoplasma yeasts. MAb GK1.5 did not alter the functional properties of murine macrophages as measured by antigen presentation, production of interleukin-1 in response to lipopolysaccharide, and phagocytosis of H. capsulatum yeasts. These results suggest that the L3T4+ T-cell subset is an essential constituent of the cell-mediated immune defense against H. capsulatum infection.
 ...
PMID:Role of L3T4+ T cells in host defense against Histoplasma capsulatum. 296 20

The role of macrophages in the innate immunity of mice to histoplasmosis was investigated using silica, which selectively inactivates macrophages. Mice given silica IV 1 day prior to challenge with live yeast cells of Histoplasma capsulatum were more susceptible to infection than were untreated controls. This increased susceptibility to Histoplasma was observed when mice were given silica at 1, 14, and 21 days prior to infection but not at 3 and 7 days. Silica treated mice that survived 30 days after challenge with a sublethal dose of Histoplasma had 23 times more viable organisms in their spleens than in those of untreated controls. The blastogenic response of spleen cells to concanavalin A and phytohemagglutinin was unaffected at 12 hr after silica injection but was significantly depressed between 1 and 21 days. In contrast, silica treatment did not affect the blastogenic response of spleen cells to lipopolysaccharide. Silica particles were cytotoxic for mouse peritoneal macrophages but not to lymphocytes in vitro. These results indicate that macrophages play an essential role in natural immunity to histoplasmosis.
 ...
PMID:Effect of silica on the susceptibility of mice to experimental histoplasmosis. 631 Jan 9

The first line of defence against natural infection by Histoplasma capsulatum (Hc) consists of bronchoalveolar macrophages (BAM) and an early inflammatory response in the lungs. Little is known about the interaction of BAM and Hc, consequently we studied murine BAM in vitro to assess their role in the pulmonary defence in histoplasmosis. A short-term 3-h assay was used to measure fungicidal activity of control BAM and interferon-gamma (IFN-gamma) plus lipopolysaccharide (LPS)-activated BAM. Fungistatic activity of BAM was determined with a 24-h assay. A method devised for measuring colony-forming units (CFU) of non-ingested non-adherent and adherent ingested yeast cells of Hc in BAM cocultures was used. Activated BAM killed Hc (reduced inoculum CFU by 25 +/- 12%; n = 4). The fungicidal activity of BAM was abrogated by 0.2 mM NG-monomethyl-L-arginine (NMMA) or catalase but not by superoxide dismutase. In fungistatic assays activated BAM inhibited multiplication of Hc by 61 +/- 4% (n = 3) compared with cocultures with control BAM. However, Hc multiplied 100% more in control BAM cocultures than in medium alone. Data indicated that this was due to advantages that Hc has in the intracellular environment. Only NMMA inhibited fungistatic activity of activated BAM. In experiments with peritoneal macrophages (PM), results similar to those with BAM were obtained. In conclusion, activated BAM and PM kill yeast cells of Hc by a mechanism dependent on hydrogen peroxide and products of the nitric oxide synthase (NOS) pathway, whereas fungistasis depends only on products of the NOS pathway.
 ...
PMID:Antifungal mechanisms of activated murine bronchoalveolar or peritoneal macrophages for Histoplasma capsulatum. 755 2