Hapten-Induced Model of Chronic Inflammation and Ulceration in the Rat Colon

HIF-1α Is Essential for Myeloid Cell-Mediated Inflammation

https://www.gastrojournal.org/article/0016-5085(84)90202-6/pdf

Quantitative assay for acute intestinal inflammation based on myeloperoxidase activity: Assessment of inflammation in rat and hamster models

Although mast cells have been implicated in a variety of inflammatory conditions including immediate hypersensitivity and interstitial cystitis, their physiological role in the body is unknown. We investigated the role of mast cells in host defence against bacterial infections using a well characterized mast-cell-deficiency mouse model. We report here that mast cells, which are selectively located at portals of bacterial entry, are important to host defence. Mast-cell-deficient WBB6F1-W/Wv mice (W/Wv) were up to 20-fold less efficient in clearing enterobacteria than control WBB6F1 +/+ (+/+) mice or mast-cell-reconstituted W/Wv (W/Wv+MC) mice. With higher bacteria inocula, only W/Wv mice died (80%). The limited bacterial clearance in W/Wv mice directly correlated with impaired neutrophil influx. The mast-cell chemoattractant TNF-alpha was implicated in the neutrophil response because TNF-alpha was locally released only in +/+ and W/Wv+MC mice, TNF-alpha-specific antibodies blocked over 70% of the neutrophil influx, and purified mast cells released TNF-alpha upon incubation with bacteria. Additionally, the type-1 fimbrial subunit, FimH, was the necessary enterobacterial component for mast-cell activation and neutrophil influx because an isogenic FimH- mutant evoked a limited neutrophil response in +/+ mice compared to wild-type bacteria.

Mast cell modulation of neutrophil influx and bacterial clearance at sites of infection through TNF-alpha

Myeloperoxidase activity as a quantitative assessment of neutrophil infiltration into ischemic myocardium.

Measurement of Cutaneous Inflammation: Estimation of Neutrophil Content with an Enzyme Marker

Summary: Newborn dogs were inoculated intratracheally with 0.5–1.0 x 108 Staphylococcus aureus/g body weight. Neutropenia (490 ± 280 neutrophils/mm3 versus 8,390 ± 490 control, ± S.E., P< 0.001), and depletion of the marrow neutrophil storage pool (3 ± 1% versus 27 ± 2% storage neutrophils P < 0.001) occurred 5–6 h following the inoculation. All animals died at 6–10 h. Additional inoculated pups were selected at random to receive transfusions of either granulocytes, plasma or red blood cells. Granulocyte transfusions (3x109 neutrophils/kg) improved survival (P < 0.005), but plasma and red blood cells did not. Speculation: Previous reports have shown that certain neonates with bacterial sepsis utilize neutrophils more rapidly than they are replaced by the marrow mitotic neutrophil pool. The quantitative neutrophil deficiency thus produced, results in blood neutropenia, reduced neutrophil availability to affected tissues and high mortality. In this study, neonatal dogs were infected experimentally and found to develop neutropenia, depletion of neutrophil reserves, and death. Granulocyte transfusions improved the survival of these animals while plasma or packed red blood cell transfusions did not. Thus, granulocyte transfusion may present a useful therapeutic modality in those septic neonates who are found to have neutropenia and a depleted neutrophil supply.

Granulocyte transfusion in septic canine neonates.

Although improvements in the management of adults with acute leukemia have lagged behind those seen in the treatment of children, there are clear reasons for optimism. Combination chemotherapy for acute myeloblastic leukemia (AML) and acute lymphoblastic leukemia (ALL) in adults results in complete remissions in 50-85% of patients. An increasing number of these patients remain in continuous remission for over two years with a significant proportion (15-25%) disease-free after five years. Those who remain in remission for more than five years have a low incidence of relapse and many may be cured. Nevertheless, there are still many problems to be solved. Improved, less toxic induction regimens are needed. The roles of maintenance, late intensification, and central nervous system prophylaxis remain unresolved. The results of bone marrow transplantation for adults with AML in remission are encouraging enough to make this an attractive form of therapy for any patient younger than age 40 with a histocompatible sibling. New forms of treatment, such as immunotherapy and monoclonal antibodies, remain investigational.

Adult acute leukemia. Aggressive treatment improves survival.

Neutrophil release and migration in mice were studied over a 24-hr period after the sc implantation of a single polyvinyl sponge. The release of neutrophils from the marrow was evaluated by directly counting the residual neutrophils in the femoral marrow of animals with sponges. Sponge and tissue neutrophil content was determined by extraction and assay of myeloperoxidase (MPO), a marker enzyme for neutrophils. A maximum depletion of 48% of the mature neutrophils in the marrow was observed 5 hr after sponge implantation, in keeping with significant release of neutrophils for migration to the sponge. The released cells were not found in the circulating granulocyte pool, since neutropenia was noted. The accumulation of neutrophils in the sponge increased throughout the 24-hr period, whereas in the tissue adjacent to the sponge maximum accumulation of neutrophils occurred within 7 hr. In fact, neutrophils migrated to at least three sites--the sponge, the skin overlying the sponge, and the skin in which an incision had been made to insert the sponge. The sponge content of neutrophils represented 0.3-33% of the neutrophils migrating to the combined lesion (sponge and skin sites). Therefore, if the neutrophil response to foreign body implantation is to be measured in its entirety, it is necessary to quantify not only the neutrophils within the foreign body but also those in the tissues surrounding it. These studies describe an animal model for neutrophil release and migration to tissues following a standard stimulus. It is proposed that this model may be useful in exploring the factors which influence the release and migration of neutrophils in vivo.

The neutrophil response to polyvinyl sponge implantation.

The mortality of septic infants approaches 80% if they exhibit neutropenia and depletion of the marrow neutrophil storage pool (% PMN + bands + metas/1000 marrow cells) (J. Peds., 1981). We postulated that GT might decrease mortality in these infants and tested this hypothesis in an animal model and clinical study. Eight newborn dogs were inoculated intratracheally with Staph aureus, developed neutropenia and died (490 ± 280 neut/mm3 vs 8,390 ± 490 in controls, x ± S.E. p 9% survived. Only one of 9 with an NSP of <6% survived. Then, neonates with sepsis, neutropenia and an NSP of <6% were randomly assigned to receive or not receive GT. Of 5 infants who did not receive GT, one survived. All 4 who received 0.2-1.0 × 109 neutrophils/kg survived (p <.05). No significant change in PaO2 (↑2 ± 2 torr), PaCO2 (↑1.5 ± 2 torr), pH (↓0.01 ± 0.01 units), or blood pressure (↑2 ± 2 mmHg) occurred with GT. All urine cultures were negative for CMV. These data support the concept that GT may be practical and effective in septic, neutrophil depleted neonates.

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Dennis A. Priebat

Papers

Measurement of Cutaneous Inflammation: Estimation of Neutrophil Content with an Enzyme Marker

Granulocyte transfusion in septic canine neonates.

Adult acute leukemia. Aggressive treatment improves survival.

The neutrophil response to polyvinyl sponge implantation.

997 granulocyte transfusions (gt) increase survival in neonates with sepsis and neutrophil depletion