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Cellular repository for blood histamine in normal and nematode-infected rats
Abstract:
Infections with the nematode N. brasiliensis is associated with a recruitment of intestinal mucosal mast cells (MMC) which increase greatly in numbers. We have studied histamine levels in the gut, whole blood and plasma in relation to MMC of the gut and blood cell morphology during the course of the infection in an attempt to clarify possible relations between circulating blood basophils and MMC. The results show a parallel increase in MMC numbers and histamine content of the gut, remaining high to day 20 after infection. Blood histamine increased from a control level of 30-40 ng/ml to a maximum of 200 ng/ml on day 12 to 14, but returned towards the control level already on day 16 after infection. There was a corresponding increase in plasma histamine to a maximum of 80 ng/ml. The total number of blood neutrophils increased during the early phase of the infection and there was a pronounced eosinophilia from day 10 to 16. No cells containing metachromatic granules were found in a screening comprised of 10,000 cells per specimen. During day 10 to 16 we found a number of coarsely granuled and vacuolated cells. The granules stained darkly by the Giemsa stain but not metachromatically with Toluidine Blue or with Alcian Blue at a low pH. We interpret this as an equivalent to the so-called toxic granulation occurring in human neutrophils. These cells may have been mistaken for basophils by previous investigators. The cellular repository for the high concentration of histamine in the blood is unknown. We suggest, as a working hypothesis, that it is contained in a circulating progenitor for MMC which has the ability to synthesize and, in a loosely bound state store, histamine, but which has not yet acquired the ability to assemble the specific metachromatic granules.
Insights
Nematode infections increase intestinal mast cells and gut histamine. Blood histamine also rises, but circulating cells resembling basophils are absent, suggesting a potential progenitor cell for mast cells.
Area of Science:
- Immunology
- Parasitology
- Cell Biology
Background:
- Nematode infections, such as N. brasiliensis, trigger a significant increase in intestinal mucosal mast cells (MMC).
- Understanding the relationship between circulating blood cells and MMC is crucial for elucidating immune responses during parasitic infections.
Purpose of the Study:
- To investigate histamine levels in the gut, blood, and plasma.
- To correlate histamine changes with MMC numbers and blood cell morphology.
- To clarify the potential relationship between circulating blood basophils and intestinal MMC.
Main Methods:
- Measurement of histamine levels in gut, whole blood, and plasma.
- Analysis of blood cell morphology.
- Quantification of intestinal mucosal mast cells (MMC) during infection.
- Differential blood cell counts and morphological examination of 10,000 cells per specimen.
Main Results:
- A parallel increase in MMC numbers and gut histamine content was observed, persisting until day 20 post-infection.
- Blood and plasma histamine levels showed a significant, transient increase, peaking around days 12-14.
- No typical basophils were identified; however, neutrophils with coarse granules and vacuolation, resembling toxic granulation, were noted and may have been misidentified in previous studies.
Conclusions:
- The study highlights a dynamic interplay between nematode infection, mast cell proliferation, and histamine release.
- The cellular source of elevated blood histamine remains unidentified, but a circulating progenitor cell for MMC is proposed as a working hypothesis.
- The findings suggest that certain blood cells might be precursors to MMC, capable of synthesizing and storing histamine prior to granule maturation.