Interaction of Inflammatory Mediators with the Lymphatic Vessel

Johnston, Mary

doi:10.1159/000157044

Cited by 10 publications

(7 citation statements)

References 30 publications

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“…However, in addition to its high susceptibility to fluid load, lymphatic vessel contractile activity is also directly altered by mediators released during the inflammatory process and which certainly gain access to the vicinity of the lymphatic vessels or to the lymphatic circulation. Data mainly obtained in vitro showed that lymphatic pumping is impaired in the presence of prostanoids (see above), nitric oxide or histamine, for example, an effect independent of their action on vascular permeability (see review by Johnston, 1987 and von der Weid, 2001). Given that proteinases are also thought to be released during inflammation, the possibility exists for activation of PARs expressed in lymphatic vessels.…”

Section: Discussionmentioning

confidence: 99%

“…Oedema formation also occurs during inflammation as a result of the action of inflammatory mediators on vascular permeability and thus elevation of interstitial fluid pressure. Although interstitial fluid pressure is critical in setting lymphatic pumping rate, the latter is also directly affected by many of the mediators released during inflammation (see review by Johnston (1987) and von der Weid (2001)). Proteinase‐activated receptors (PARs), are a family of G protein‐coupled receptors that are activated by the proteolytic cleavage of their extracellular amino terminus, unmasking a tethered ligand (Vu et al 1991).…”

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confidence: 99%

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Proteinase‐activated receptor 2 activation modulates guinea‐pig mesenteric lymphatic vessel pacemaker potential and contractile activity

Chan¹,

Vergnolle²,

Hollenberg³

et al. 2004

The Journal of Physiology

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Lymphatic vessels rhythmically constrict to avoid fluid and protein accumulation in the interstitial space. This activity is critical during inflammation to prevent excessive oedema. Lymphatic pumping is intrinsic to the smooth muscle in the vessel wall and is due to the spontaneous occurrence of action potentials, the pacemaker of which is proposed to be spontaneous transient depolarizations (STDs). This function is highly susceptible to the fluid load and modulated by chemical agents, amongst which inflammatory mediators are important players. Activation of proteinase-activated receptors (PARs) has been involved in inflammation and affects vascular smooth muscle tone. The present study aims to investigate the role of PAR 2 , a member of the PAR family, in lymphatic vessel pumping. RT-PCR experiments revealed that PAR 2 message is present in lymphatic vessels of the guinea-pig mesentery. Agonists of PAR 2 such as trypsin and the activating peptide, SLIGRL-NH 2 , caused a decrease in the contractile activity of intraluminally perfused lymphatic vessels. Moreover, intracellular microelectrode recordings from isolated vessels revealed that PAR 2 activation hyperpolarized the lymphatic smooth muscle membrane potential and altered STD amplitude and frequency. The decreases in constriction frequency and STD activity as well as the hyperpolarization were dependent on a functional endothelium, not affected by NO synthase or guanylyl-cyclase inhibition, but mimicked by PGE 2 and iloprost and blocked by indomethacin (10 µM) and glibenclamide (1 µM). These results show that PAR 2 activation alters guinea-pig lymphatic vessel contractile and electrical activity via the production of endothelium-derived cyclo-oxygenase metabolites.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Proteinase‐activated receptor 2 activation modulates guinea‐pig mesenteric lymphatic vessel pacemaker potential and contractile activity

Chan¹,

Vergnolle²,

Hollenberg³

et al. 2004

The Journal of Physiology

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“…The clearance of radiolabeled albumin from intradermal or subcu taneous tissues has been interpreted as a measure of lymphatic drainage [Hamilton et al, 1986; for details on the active role of lymphatics in inflammation, see Johnston, 1987]. Colditz and Movat [1984c] noted that the retention of intradermally injected l25I-serum albumin was the same at sites rein jected with a chemotaxin as in normal sites and thus more rapid clearance of the chemo taxins could not account for the reduced number of neutrophils at reinjected sites.…”

Section: Chemotactic Factorsmentioning

confidence: 99%

Neutrophil Emigration and Microvascular Injury

Movat

Cybulsky²

1987

Path Immunopathol Res

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“…These alterations are thought to impair lymph drainage, though experimental validation is still required. A possible mechanism by which lymphatic pumping is altered during the inflammatory process is via the action of inflammatory mediators, many of which have vasoactive properties and are present in the lymphatic surroundings and/or in the lymph (reviewed in Johnston, 1987; von der Weid, 2001). Indeed, in the study by Wu et al (2006), we demonstrated a role for metabolites of the cyclooxygenase pathway in the ileitis‐induced inhibition of lymphatic pumping.…”

Section: Introductionmentioning

confidence: 99%

Mechanisms of VIP‐induced inhibition of the lymphatic vessel pump

Weid

Rehal

Dyrda

et al. 2012

The Journal of Physiology

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Key points• Lymphatic pumping is characterized by the ability of collecting lymphatic vessels to contract in a phasic manner to propel lymph. This activity is critical for tissue fluid homeostasis and immune cell transport to lymph nodes.• Vasoactive intestinal peptide (VIP) is a neuro-immuno-modulator with anti-inflammatory properties released by peptidergic nerves and by inflammatory cells patrolling the interstitium and lymph.• Here we report that VIP is present in lymphatic vessels as well as in the lymph and that it potently inhibits lymphatic pumping and hyperpolarizes the lymphatic muscle via stimulation of VPAC2 VIP receptors, activation of protein kinase A and opening of ATP-sensitive K + channels.• These results suggest an important role for VIP in inhibiting lymphatic pumping. This process might become critical during inflammation, where it would lead to decreased lymph drainage, oedema formation and compromised immune cell trafficking.Abstract Lymphatic vessels serve as a route by which interstitial fluid, protein and other macromolecules are returned to the blood circulation and immune cells and antigens gain access to lymph nodes. Lymph flow is an active process promoted by rhythmical contraction-relaxation events occurring in the collecting lymphatic vessels. This lymphatic pumping is an intrinsic property of the lymphatic muscles in the vessel wall and consequent to action potentials. Compromised lymphatic pumping may affect lymph and immune cell transport, an action which could be particularly detrimental during inflammation. Importantly, many inflammatory mediators alter lymphatic pumping. Vasoactive intestinal peptide (VIP) is a neuro-and immuno-modulator thought to be released by nerve terminals and immune cells in close proximity to lymphatic vessels. We demonstrated the presence of the peptide in lymphatic vessels and in the lymph and examined the effects of VIP on mesenteric collecting lymphatic vessels of the guinea pig using pharmacological bioassays, intracellular microelectrode electrophysiology, immunofluorescence and quantitative real-time PCR. We showed that VIP alters lymphatic pumping by decreasing the frequency of lymphatic contractions and hyperpolarizing the lymphatic muscle membrane potential in a concentration-dependent manner. Our data further suggest that these channels. Inhibition of lymphatic pumping by VIP may compromise lymph drainage, oedema resolution and immune cell trafficking to the draining lymph nodes.

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Interaction of Inflammatory Mediators with the Lymphatic Vessel

Cited by 10 publications

References 30 publications

Proteinase‐activated receptor 2 activation modulates guinea‐pig mesenteric lymphatic vessel pacemaker potential and contractile activity

Proteinase‐activated receptor 2 activation modulates guinea‐pig mesenteric lymphatic vessel pacemaker potential and contractile activity

Neutrophil Emigration and Microvascular Injury

Mechanisms of VIP‐induced inhibition of the lymphatic vessel pump

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