Itching for Answers: How Histamine Relaxes Lymphatic Vessels

Abstract

In the current issue of Microcirculation, studies by Kurtz et al. and Nizamutdinova et al. together provide new evidence supporting a role for histamine as an endothelial-derived molecule that inhibits lymphatic muscle contraction. In particular, Nizamutdinova et al. show that the effects of flow-induced shear stress on lymphatic endothelium are mediated by both nitric oxide and histamine, since only blockade of both prevents contraction strength and frequency from being altered by flow. Separately, Kurtz et al. used confocal microscopy to determine a preferential expression of histamine receptors on the lymphatic endothelium and demonstrated that histamine applied to spontaneously contracting collecting lymphatics inhibits contractions. Previous studies disagreed on whether histamine stimulates or inhibits lymphatic contractions, but also used differing concentrations, species, and preparations. Together these new reports shed light on how histamine acts within the lymphatic vasculature, but also raise important questions about the cell type on which histamine exerts its effects and the signaling pathways involved. This editorial briefly discusses the contribution of each study and its relevance to lymphatic biology.

Persistent popliteal lymphatic muscle cell coverage defects despite amelioration of arthritis and recovery of popliteal lymphatic vessel function in TNF-Tg mice following anti-TNF therapy

“…Along with damaged LMCs identified by ultrastructural imaging, the LECs were also found to be apoptotic in the PLVs of TNF-Tg mice with severe arthritis 9 . These findings suggest that the cellular contribution to lymphatic function is a complex and dynamic phenomenon where multiple cell types (i.e., LMCs, LECs, macrophages, mast cells 34 , 35 , etc.) may be involved, and future investigation into the interactions of these peri-lymphatic cells during inflammation and therapy is warranted.…”

Distinct mast cell subpopulations within and around lymphatic vessels regulate lymph flow and progression of inflammatory-erosive arthritis in TNF-transgenic mice

“…The literature describes two subtypes of mast cells: mucosal mast cells that produce tryptase and connective tissue mast cells that produce chymase, tryptase, and carboxypeptidases (20). Mast cells are recognized as potent regulators of lymphatic vessel function based on their anatomical proximity and ability to produce, store, and release various inflammatory and vasoactive mediators (21)(22)(23). Mast cells release mediators (e.g., histamine) that impact the contractility of lymphatic vessels (21,23,24), which is critical for efficient drainage of joint inflammation.…”