Histamine production by human neutrophils

Abstract

Histamine is an important mediator in the development of allergic reactions. Only a small subset of human cell types is able to produce histamine. No previous studies have shown that human neutrophils are among them. The present work was undertaken to analyze whether human neutrophils produce histamine, and to determine what agonists are involved in histamine production by human neutrophils. The expression of histidine decarboxylase in human neutrophils was established by quantitative PCR, Western blotting, and flow cytometry analysis. The activity of the enzyme was determined by ELISA, which measured histamine in the culture supernatant of neutrophils stimulated with a set of classical agonists. Human neutrophils are bona fide histamine-producing cells. Neutrophils store ∼0.29 pg/cell and release ∼50% of the histamine content in an antigen-dependent manner and on stimulation with other neutrophil agonists. Basal expression of histidine decarboxylase, the rate-limiting enzyme in histamine production, is higher in neutrophils from patients with allergies than from healthy donors. Our results cannot be ascribed to cell contamination for several reasons. LPS failed to induce histamine release by basophils, whereas it induced histamine release by neutrophils; and we did not detect basophils, monocytes, or lymphocytes in our neutrophil preparations. Eosinophils, albeit detected, were only 0.001-0.004% of the final cell population, and they did not store or release histamine on antigen or LPS stimulation. Antigens to which patients with allergies were sensitized stimulated release of histamine from neutrophils. These observations represent a novel view of neutrophils as possible source of histamine in the allergic diseases.

Bone Marrow Myeloid Cells Regulate Myeloid-Biased Hematopoietic Stem Cells via a Histamine-Dependent Feedback Loop

“…In particular, TLR2/4/6 genes were highly enriched in granulocytic myeloid cells (Figure 2B and S3C) (Table S1) (Chen et al, 2017). As LPS elicits histamine release from Hdc-expressing cells (Alcaniz et al, 2013), we analyzed histamine release from Hdc-GFPhi HSCs and myeloid cells in response to in vitro LPS stimulation. The results showed that only Hdc-GFP hi myeloid cells were capable of releasing a large amount of histamine shortly after LPS treatment (Figure S3D), indicating that Hdc-expressing myeloid cells preferentially sense and respond to bacteria-mediated TLR signals.…”

The histamine H4 receptor mediates inflammation and Th17 responses in preclinical models of arthritis

“…It is important to note that the H 4 R has a very high affinity for histamine, especially compared with the histamine H 1 and H 2 receptors, and therefore it may be activated by cells that release even low levels of histamine. To this point, it has become apparent that many immune cells, such as dendritic cells, T cells and neutrophils, are capable of producing histamine when stimulated 7 30 31. It has been speculated that local production of histamine by dendritic cells can act in an autocrine fashion to modulate dendritic cell/T cell interactions,32 and this local production of histamine in the joint or at sites of T cell activation may be the most relevant for H 4 R activation in human arthritis.…”

Analysis of Histamine Receptor Knockout Mice in Models of Inflammation

“…In mast cells, basophils, enterochromaffin-like cells of the gastrointestinal tract, and histaminergic neurons, histamine is stored, probably heparin-bound, in granules and is released in response to a specific stimulus (Barnes et al, 1988;Rabenstein et al, 1998). However, HDC is expressed not only in these "classically" known histamine-producing cells but also in monocyte-derived cells (László et al, 2000;Dunford et al, 2006;Xu et al, 2012;Alcañiz et al, 2013). As a consequence, one can speculate that HDC activity is present, at least after induction, in virtually every other cell type as well.…”