Mast cells induce upregulation of P‐selectin and intercellular adhesion molecule 1 on carotid endothelial cells in a new in vitro model of mast cell to endothelial cell communication

Abstract

Summary It is suggested that mast cells contribute to cell recruitment in inflammation through the upregulation of endothelial adhesion molecules. P-selectin and intercellular adhesion molecule (ICAM)-1 are two key adhesion molecules that have been associated indirectly with mast cell activity. The canine C 2 mastocytoma cell line and primary cultures of canine carotid endothelial cells were used to establish a new in vitro model to help study the interaction between mast cells and endothelial cells. Carotid endothelial cells were incubated with mast cell mediators to uncover their effect on endothelial ICAM-1 and P-selectin expression. To assess the relative contributions of tumour necrosis factor (TNF)-α and histamine to such effect, an H 1 antihistamine and a TNF-α blocking antibody were used. Prior to activation by mast cell mediators, P-selectin was expressed only within the cytoplasm, and ICAM-1 was constitutively expressed on the surface of the canine carotid endothelial cells. Both adhesion molecules were enhanced significantly and strongly upon mast cell activation at various time points. Unstored TNF-α was fully responsible for ICAM-1 upregulation. P-selectin was up-regulated by both preformed and newly synthesized mast cell mediators, but neither histamine nor TNF-α accounted for such an effect. Therefore, a new model is proposed in which the pro-inflammatory effect of mast cells on endothelial cells can be studied in vitro. In this model, it has been demonstrated that only TNF-α accounts for the overexpression of ICAM-1 induced by mast cells, and that mast cells up-regulate P-selectin expression through a histamine-independent mechanism.

The role of mast cells in atopy: what can we learn from canine models? A thorough review of the biology of mast cells in canine and human systems

“…Preformed and induced tumour necrosis factor (TNF)‐ α has been observed in canine mastocytoma cell lines 151 . We showed that this is responsible for the upregulation of intercellular adhesion molecule‐1 (ICAM‐1) by canine endothelial cells 152 . Along those lines, TNF‐ α derived from cardiac mast cells may also be a crucial factor in upregulating interleukin (IL)‐6 expression in infiltrating leucocytes, and initiating the cytokine cascade responsible for myocyte expression of ICAM‐1 101 .…”

Regulation of Endothelial Cell Adhesion Molecule Expression by Mast Cells, Macrophages, and Neutrophils

“…For example, mast cell-derived histamine, neutrophil elastase, tryptase, substance P, and angiotensin-II increase endothelial adhesion molecule expression and leukocyte rolling, adhesion, and emigration. Pre-treatment with function blocking monoclonal antibodies to adhesion molecules [21] or cytokines [22] reduces these leukocyte responses.…”

“…Mast cell–deficient ( Kit W-sh/W-sh ) mice were protected from diet-induced atherosclerosis [23]. Atherosclerotic lesions in these mice contained fewer macrophages and T-cells, suggesting reduced leukocyte recruitment occurred in the absence of mast cells [22]. In a separate study, we used the same mice and tested the role of mast cells in white adipose tissue growth.…”

The diversity of myeloid immune cells shaping wound repair and fibrosis in the lung

“…After injury, activated mast cells immediately release several pro‐inflammatory mediators to recruit other immune cells, such as neutrophils, into the wound (Hart, ). Mast cells can also contribute to the proliferative phase by secreting several growth factors such as VEGF, bFGF, and PDGF to stimulate endothelial cells (Torres et al., ; Zhang et al., ). Furthermore, during remodeling, mast cells promote fibroblast migration, proliferation, and differentiation into myofibroblasts through production of TGF‐β, PDGF, tryptase, and histamine (Artuc, Steckelings, & Henz, ).…”