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Macrophages have been described as ‘factories’ of pro‐inflammatory cytokines. Several years ago the present investigators reported that binding of inactive myeloperoxidase (iMPO) to the macrophage‐mannose receptor resulted in the induction of TNF and other cytokines. Also, if endothelial cells were incubated with iMPO, but not enzymatically active myeloperoxidase (MPO), upregulation of cytokine mRNA and cytokines was observed. Taken in their entirety, the data suggest a dichotomy of function for myeloperoxidase; that is, enzymatically active MPO functions primarily in cell killing through the ‘cytotoxic triad’ and iMPO functions as an immunoregulatory molecule through the induction of numerous cytokines. These studies underscore a previously unrecognized interaction among neutrophils, endothelial cells and macrophages, resulting in the induction of TNF and perpetuation of inflammation. The inflammation induced could be relevant in a number of diseases in which neutrophils play a prominent role. The importance of this interaction in the pathogenesis of rheumatoid arthritis is currently under investigation.

Inflammation of the lung is characterized by the influx of increased numbers of various leukocytes including polymorphonuclear leukocyte (PMN) neutrophils. In addition to cells, numerous studies have pointed to the role of tumor necrosis factor-alpha in the inflammatory process. This study addresses a previously unrecognized interaction between neutrophil-derived myeloperoxidase (MPO) and resident alveolar macrophages (AMø). Rat AMø exposed to either enzymatically active recombinant MPO or enzymatically inactive MPO (iMPO) exhibited an increased respiratory burst (RB). When iMPO was employed, the enhancement of the RB was greater than that observed with MPO. Although the RB was greater with iMPO, macrophage (Mø)-mediated intracellular candidic activity was equivalent for both MPO and iMPO. It is known that pro- inflammatory cytokines contribute to the inflammatory process. When rat AMø were exposed to both forms of myeloperoxidase, iMPO demonstrated greater upregulation of cytokine genes as well as product. These data suggest that at the site of inflammation, neutrophil-derived MPO and iMPO stimulate AMø, resulting in an increased inflammatory and cytotoxic state, and thereby contributing to the general lung inflammatory response.

Candida albicans is an opportunistic pathogen whose resurgence coincides with the rising number of AIDS patients. Neutrophils are known to be involved in the clearance of Candida infections; however, the role of macrophages in host defenses against this organism is not well understood. The present study was undertaken to examine an unrecognized interaction between neutrophils and macrophages resulting in enhanced killing of candidae in vitro. Murine peritoneal macrophages exposed to recombinant myeloperoxidase exhibited enhancement of the respiratory burst, increased phagocytosis, and a dose-dependent increase in intracellular killing of Candida species. Radical scavengers reduced the killing, indicating a role of reactive oxygen intermediates in the candidacidal activity observed. These data suggest that at the site of infection, myeloperoxidase released from neutrophils activates macrophages and induces microbicidal activity.

It is known that a peroxidase, H sub(2)O sub(2), and a halide form a \"cytotoxic triad.\" As a result of the interactions of the components of the triad, reactive oxygen intermediates (ROI) are formed that help to destroy various invading pathogens including Candida. The present study was undertaken to determine if equivalent units of peroxidase induced equivalent levels of macrophage-mediated killing of Candida. Murine peritoneal macrophages were exposed to various concentrations of eosinophil peroxidase (EPO), myeloperoxidase (MPO), and horseradish peroxidase (HRP). Luminol-dependent chemiluminescence studies showed that equivalent units of peroxidase, as determined by oxidation of guaiacol, demonstrated a hierarchical pattern of ROI production. Macrophage phagocytosis and candidicidal activity, as measured by a fluorescence acridine orange assay, also demonstrated the same hierarchical pattern of EPO > MPO > HRP. Therefore, enzymatically equivalent peroxidases do not demonstrate equivalent candidicidal activity. These data indicate a distinct order of peroxidases relative to their ability to stimulate chemiluminescence and macrophage-mediated killing.

Supervisor Jerry Brown noticed the 1994 Ford Explorer missing between 4 and 6 a.m., and authorities from Nassau County to the FBI and Secret Service were investigating the case. Brown had no idea why his vehicle was a target for car theft, but was worried about bigger concerns. Since the Sept. 11 terrorist attacks, the FBI has warned area authorities about the possibility of people stealing emergency vehicles. Rosalie Pascale, 60, of 1918 Haight Ave. in the Morris Park section of the Bronx, was standing on a chair while trying to dislodge the air conditioner from the window about 6 p.m. Saturday, police said.