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Biomedical subjects

J A Lincoln

Publications and source records attributed to J A Lincoln.

11 recordsLinked to original sources
PubMed1999

Enzymatically inactive eosinophil peroxidase inhibits proinflammatory cytokine transcription and secretion by macrophages.

The present investigators have reported previously that macrophages (Mphi) can bind either myeloperoxidase (MPO) or eosinophil peroxidase (EPO) resulting in enhanced cytotoxicity to Candida albicans. Since MPO was shown to be immunomodulatory, the present study was initiated to determine whether either EPO or partially fragmented EPO (fgEPO) also modulated cytokine secretion. Murine peritoneal Mφ simultaneously stimulated with fgEPO and one of the following, (1) LPS, (2) mannosylated bovine serum albumin (mBSA), (3) interferon-gamma (IFN-gamma), or (4) Poly I:C, demonstrated both dose- and time-dependent decreases in TNF-alpha and IL-6 and a dose-dependent decrease in IFN-alpha/beta. The mRNA levels of Mphi exposed to fgEPO and mBSA demonstrated that fgEPO modulated Mphi cytokine function by decreasing TNF-alpha and IL-6 mRNA transcripts without altering transcription of TGF-beta or GM-CSF. These results demonstrate a possible interaction between the Mphi and eosinophil that could result in reduction of inflammation.

Animals↗
PubMed1997

Upregulation of phagocytosis and candidicidal activity of macrophages exposed to the immunostimulant acemannan.

Previous studies by these investigators have shown that mannosylated bovine serum albumin (m-BSA) enhances the respiratory burst (RB), phagocytosis, and killing of Candida albicans by resident murine peritoneal macrophages (MO). Upregulation of the above MO functions was associated with binding of m-BSA to the MO-mannose receptor. The present study was done to determine if the immunostimulant, acemannan prepared from aloe vera, could stimulate MO in a similar manner. Resident peritoneal MO collected from C57BL/6 mice were exposed to acemannan for 10 min. The RB was measured using chemiluminescence and demonstrated approximately a two-fold increase above the media controls. In studies involving phagocytosis, MO were exposed to acemannan, washed and exposed to Candida at a ratio of 1:5. The percent phagocytosis and Candida killing were determined using fluorescence microscopy. There was a marked increase in phagocytosis in the treated cultures (45%) compared to controls (25%). Macrophages exposed to acemannan for 10 min resulted in ca 38% killing of Candida albicans compared with 0-5% killing in controls. If MO were incubated with acemannan for 60 min, 98% of the yeast were killed compared to 0-5% in the controls. The results of the present study indicate that short term exposure of MO to acemannan upregulates the RB, phagocytosis and candidicidal activity. Further studies are needed to clarify the potential use of this immunostimulant as an anti-fungal agent.

Adjuvants, Immunologic↗
PubMed1997

Macrophage-mediated candidacidal activity is augmented by exposure to eosinophil peroxidase: a paradigm for eosinophil-macrophage interaction.

Various disease states are associated with eosinophilia and the release of eosinophil peroxidase (EPO) into the microenvironment. The present study targets the effects of low levels of EPO on macrophage (M phi) phagocytosis and intracellular killing of Candida albicans as well as M phi oxidative activity measured as the luminescence product of luminol dioxygenation. Resident murine peritoneal M phi were exposed to various concentrations of EPO. Chemiluminescence data indicate that nanomolar concentrations of EPO markedly enhanced the dioxygenation activity (respiratory burst) of M phi. In other studies, the exposure of M phi to 0.17 microM EPO for 10 min. enhanced M phi-mediated candidacidal activity 10 fold. The above data indicate that EPO enhances certain M phi functions. Also the results illustrate a previously un-recognized interaction between eosinophils and M phi and implicate yet another possible role for EPO in host defenses against disease.

Animals↗
PubMed1997

Enhancement of macrophage-mediated bactericidal activity by macrophage-mannose receptor-ligand interaction.

Neutrophils represent one of the host's primary defenses against invading organisms. These cells often arrive at the site of infection prior to macrophages (M phi). Neutrophils release myeloperoxidase (MPO) into the micro-environment during phagocytosis. Previous studies by the present investigators have shown that M phi bactericidal activity is enhanced by exposure to MPO. A recent report suggests that as much as 40% of this protein is enzymatically inactive once it is released into the micro-environment. In the present study, exposure of M phi to an enzymatically inactive form of MPO (iMPO) or another mannosylated protein, mannosylated bovine serum albumin (mBSA), can induce the same enhanced Mø-mediated bacterial cell killing observed with the active form of MPO. Furthermore, this phenomenon is limited as galactosylated BSA (gBSA) did not induce enhancement of bacterial killing. The data suggest that interaction of either enzymatically active or inactive mannosylated proteins with the M phi mannose receptor (MMR), is sufficient to enhance M phi bactericidal activity and further underscores the binding of the MMR and resultant responses as a major host defense mechanism.

Animals↗
PubMed1995

Exogenous myeloperoxidase enhances bacterial phagocytosis and intracellular killing by macrophages.

It is well documented that myeloperoxidase (MyPo) contributes to the bacterial activities of neutrophils and monocytes. Since mature macrophages (M phi) are devoid of this enzyme, its participation in M phi-mediated phagocytes and bacterial killing has not been completely defined. The present study demonstrates the exogenously added MyPo, at physiological levels, enhances both phagocytosis and killing of Escherichia coli. Murine peritoneal M phi were exposed to various concentrations of MyPo for different time intervals. Viable opsonized E. coli was added either prior to or after addition of MyPo. Thioglycolate-induced but not resident M pho exhibited an increase in the number of phagocytizing cells. Both resident and thioglycolate-induced M phi demonstrated increased bactericidal activity. Physiological levels of soluble MyPo also induced a significant increase in chemiluminescence. Since luminol-dependent chemiluminescence measures reactive oxygen intermediate production, studies were done to determine whether superoxide anion or H2O2 was involved in MyPo-induced M pho killing. Both superoxide dismutase and catalase ablated MyPo-induced bactericidal activity. The above data suggest that soluble MyPo, released from neutrophils at a site of infection or inflammation, can enhance both phagocytosis and killing of microorganisms.

Animals↗
PubMed1976

Selecting a few residents from many applicants: a new way to be fair and efficient.

Selection of residents from among the large number of qualified applicants is an annual task requiring a significant commitment of resources by teaching hospitals. A method based on sound principles of decision-making and utilizing a computer analysis for initial ranking of applicants was developed to improve the selection process. The result was satisfactory selection with significant savings of time and effort for the residency program faculty.

Decision Making↗