Control of mast-cell 5-lipoxygenase.

Leukotrienes (LTs) from mast cells make important contributions to early events in inflammation. Therefore, the control of their 5-lipoxygenase was studied. We observed that culture conditions can significantly alter LT synthesis and intracellular 5-lipoxygenase levels.

Bacteria--Mast Cell Interactions in Inflammatory Disease.

Chronic inflammatory diseases of the gastrointestinal tract such as ulcerative colitis and Crohn's disease are characterized by mast cell proliferation and secretion of inflammatory mediators. The determinant(s) responsible for stimulating mast cells in the intestinal mucosa is not known. We investigated the interaction of mast cells with type 1 fimbriated Escherichia coli, an opportunistic pathogen and a constituent of the normal indigenous microflora of the gut.

The Role of Mast Cells and Their Mediators in IgG-Antigen Complex-Mediated Inflammation.

The strategic localization of mast cells near blood vessels led us to investigate the involvement of these cells in IgG-antigen complex-mediated inflammation, using mast-cell-deficient mice and their congenic controls. Mast cells were extensively degranulated and contributed to neutrophil influx, plasma exudation, fibrin deposition, edema formation, and tissue damage. Leukotrienes and the tumor necrosis factor (TNF) from mast cells participated in neutrophil elicitation, and histamine and leukotrienes in plasma exudation, fibrin deposition, and edema formation.

Interleukin 8 and mast cell-generated tumor necrosis factor-alpha in neutrophil recruitment.

In the reverse passive Arthus reaction in mouse skin and immune injury of mouse dermal basement membrane, neutrophil (PMN) infiltration in mast cell deficient WBB6F1-W/Wv (W/Wv) mice was only 40% of that in WBB6F1-(+)/+ (+/+) mice that had a normal mast cell repertoire. An anti-tumor necrosis factor-alpha (TNF-alpha) monoclonal antibody (mAb) decreased PMN infiltration by 35-80% in +/+ but not W/Wv mice. In addition, an anti-human interleukin-8 (IL-8) MAb, DM/C7, inhibited PMN infiltration of the skin induced by either intradermal administration of recombinant human IL-1 beta or immune complex deposition.

Mast cell degranulation induced by type 1 fimbriated Escherichia coli in mice.

The strategic location of mast cells at the host-environment interface and their ability to release potent mediators of inflammation have suggested that these cells may play a pivotal role in host defense against bacterial infection. The ability of the opportunistic pathogen, Escherichia coli, to induce degranulation of mast cells obtained from the mouse peritoneum was investigated. We determined that unlike a mutant derivative deficient in the FimH subunit of the fimbriae or nonfimbriated E.