Activation of Th lymphocytes alters pattern expression and cellular location of VIP receptors in healthy donors and early arthritis patients

We aimed to evaluate the direct action of VIP on crucial molecules involved in human osteoclast differentiation and function. We also investigated the relationship between VIP serum levels and bone remodeling mediators in early arthritis patients. The expression of VIP receptors and osteoclast gene markers in monocytes and in vitro differentiated osteoclasts was studied by real-time PCR. NFATc1 activity was measured using a TransAM® kit. Osteoclastogenesis was confirmed by quantification of tartrate-resistant acid phosphatase positive multinucleated cells. OsteoAssay® Surface Multiple Well Plate was used to evaluate bone-resorbing activity. The ring-shaped actin cytoskeleton and the VPAC1 and VPAC2 expression were analyzed by immunofluorescence. We described the presence of VIP receptors in monocytes and mature osteoclasts. Osteoclasts that formed in the presence of VIP showed a decreased expression of osteoclast differentiation gene markers and proteolytic enzymes involved in bone resorption. VIP reduced the resorption activity and decreased both β3 integrin expression and actin ring formation. Elevated serum VIP levels in early arthritis patients were associated with lower BMD loss and higher serum OPG concentration. These results demonstrate that VIP exerts an anti-osteoclastogenic action impairing both differentiation and resorption activity mainly through the negative regulation of NFATc1, evidencing its bone-protective effects in humans.

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AB0107 The Expression of VIP Receptors, VPAC1 and Vpac2, is Related to Disease Activity in Patients with Early Arthritis

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2014-eular.3472 ◽

2014 ◽

Vol 73 (Suppl 2) ◽

pp. 839.2-839

Author(s):

A.M. Ortiz ◽

L. Piris ◽

I. González-Άlvaro ◽

I.V. Seoane ◽

A. Lamana ◽

...

Keyword(s):

Disease Activity ◽

Early Arthritis ◽

Vip Receptors

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Age-Related Differences in Percentages of Regulatory and Effector T Lymphocytes and Their Subsets in Healthy Individuals and Characteristic STAT1/STAT5 Signalling Response in Helper T Lymphocytes

Journal of Immunology Research ◽

10.1155/2015/352934 ◽

2015 ◽

Vol 2015 ◽

pp. 1-13 ◽

Cited By ~ 16

Author(s):

Marija Holcar ◽

Aleš Goropevšek ◽

Alojz Ihan ◽

Tadej Avčin

Keyword(s):

Flow Cytometry ◽

T Lymphocytes ◽

Lymphocyte Subsets ◽

Healthy Individuals ◽

Helper T Lymphocytes ◽

Age Related ◽

Healthy Donors ◽

Adolescents And Adults ◽

Age Related Changes ◽

Th Lymphocytes

The dynamic process of the development of the immune system can in itself result in age-related immune malfunctions. In this study, we analysed lymphocyte subsets in the peripheral blood of 60 healthy donors, divided into groups of children, adolescents, and adults, focusing on effector (Teff) and regulatory (Treg) T lymphocytes and STAT1/STAT5 signalling response in helper T lymphocytes (Th) in adults, using flow cytometry. Our results demonstrate a decrease in the percentage of total Tregs and an increase in the percentage of total Teffs with age and a consequential immense increase in the Teff/Treg ratio. The increase of Teffs was most apparent in Th1, Th1Th17, and Th17CD161− subsets. Significant Th lymphocyte STAT1 expression differences were observed between children and adolescents, which were associated with the decrease in activated Tregs. Higher expression of STAT1 was found in FoxP3hi than in FoxP3low Th lymphocytes, while significant IL-2 induced STAT5 phosphorylation differences were found among the subsets of Th lymphocytes in adults. Our study demonstrates age-related changes in circulating Teff and Treg, as well as significant differences in STAT5/STAT1 signalling among FoxP3+ Th lymphocytes, providing new advances in the understanding of immunosenescence.

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New Recommendations Target Management of Early Arthritis

Internal Medicine News ◽

10.1016/s1097-8690(07)70202-0 ◽

2007 ◽

Vol 40 (5) ◽

pp. 13

Author(s):

NANCY WALSH

Keyword(s):

Early Arthritis ◽

Target Management

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Ultrasound Predicted Outcomes of Early Arthritis

Internal Medicine News ◽

10.1016/s1097-8690(10)70636-3 ◽

2010 ◽

Vol 43 (12) ◽

pp. 58

Author(s):

SARA FREEMAN

Keyword(s):

Early Arthritis

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Preparation and Standardization of a Stable AHF Plasma

Thrombosis and Haemostasis ◽

10.1055/s-0038-1651220 ◽

1968 ◽

Vol 19 (03/04) ◽

pp. 423-429 ◽

Cited By ~ 4

Author(s):

G. M Thelin ◽

Keyword(s):

Moisture Content ◽

Primary Standard ◽

Healthy Male ◽

Healthy Donors ◽

Fresh Plasma

SummaryA stable, lyophilized AHF reference plasma has been prepared from pooled plasma from at least 50 normal healthy donors and standardized against a primary standard of fresh plasma from 20 healthy male donors aged 20 to 40. Average AHF potency of a typical lot is 98.8%, and moisture content is less than 0.5%. Under storage at -25° C, this AHF reference plasma is stable for at least 18 months. It has been used in several major coagulation laboratories, and has given consistently satisfactory and reproducible results in AHF assays.

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Antithrombin III Antigen in Human Platelets

Thrombosis and Haemostasis ◽

10.1055/s-0038-1660078 ◽

1985 ◽

Vol 54 (03) ◽

pp. 599-602 ◽

Cited By ~ 2

Author(s):

M Léon Alhenc-Gelas ◽

M Aiach ◽

A Gorenflot ◽

J P Andreux

Keyword(s):

Arachidonic Acid ◽

Enzyme Immunoassay ◽

Antithrombin Iii ◽

Human Platelets ◽

Mean Value ◽

Normal Blood ◽

Freezing And Thawing ◽

Healthy Donors ◽

At Iii ◽

Storage Granules

SummaryImmunoreactive AT III was found in human platelets. AT III antigen was quantified in platelets taken from each of 17 healthy donors by a specific competitive enzyme immunoassay using purified AT III and AT III antibodies. AT III antigen levels in extracts of washed platelets disrupted by freezing and thawing ranged from 32 to 140 ng per 109 platelets with a mean value of 70.3 ± 27.3. When stimulated by arachidonic acid, the platelets released AT III antigen together with immunoreactive fibrinogen. These results show that AT III is present in platelets at a level corresponding to approximately 0.01% of total antithrombin in normal blood, and suggest that platelet AT III, like fibrinogen, is contained in the storage granules.

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