Increased hyaluronic acid is associated with dermal delayed-type hypersensitivity

Campbell, R D; Love, Samuel H.; Whiteheart, Sidney W.; Young, Bernadette C.; Myrvik, Quentin N.

doi:10.1007/bf00916405

Cited by 19 publications

(8 citation statements)

References 10 publications

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“…Increased circulating hyaluronate has been found in rheumatoid arthritis and in that disease a high correlation has been reported between serum hyaluronate, on the one hand, and the serum levels of haptoglobin, aj-antitrypsin and orosomucoid, on the other, all of which are increased in active inflammatory processes (Engstrom- Laurent & Hallgren, 1985). Increased hyaluronate has been found in the inflamed skin associated with A.Lundin et al delayed hypersensitivity reactions induced by PPD (tuberculin), whereas no increase has been observed in relation to granuloma formation (Campbell et al, 1982) or to irritant dermatitis (Poulsen & Cramers, 1983). The synovial fiuid in infiammatory arthritis also contains increased amounts of hyaluronate (Sundblad, 1965).…”

Section: Discussionmentioning

confidence: 97%

Circulating hyaluronate in psoriasis

et al. 1985

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A radioassay method allowing measurements of low concentrations of circulating hyaluronate was used in a study of serum hyaluronate concentrations in 44 patients with psoriasis. Twenty-three of them had only skin lesions and 21 had both skin lesions and arthropathy. In both of these groups significantly elevated serum levels of hyaluronate were found. The highest values were observed in those with widespread and active skin disease and/or active arthritis. Serum hyaluronate positively correlated with the plasma concentrations of alpha 1-antitrypsin and haptoglobin and also with ESR, which may indicate a relationship between acute inflammation and increased production of hyaluronate. Seven patients with widespread atopic dermatitis included for comparison had normal hyaluronate values. In blister fluid from lesional skin in two patients with acute psoriasis, very high concentrations of hyaluronate were found, in comparison with the concentrations in blister fluid from non-involved skin. The increased concentration of serum hyaluronate in psoriasis indicates involvement of dermal and synovial tissue in psoriasis, in addition to the epidermal changes.

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Section: Discussionmentioning

confidence: 97%

Circulating hyaluronate in psoriasis

et al. 1985

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“…Alterations in the level of expression of HA either within tissues or in body fluids has been frequently associated with inflammatory and degenerative arthropathies and other chronic inflammatory conditions in humans (61-66) and in animal models (67,68). The relationship of the association of elevated circulating HA levels in autoimmune states to the findings presented here bears further investigation, but it is attractive to speculate that this may in part derive from elevated HA expression and production on endothelial surfaces at chronically inflamed sites, and could potentially be involved in the regulation of adhesion interactions in vivo.…”

Section: Discussionmentioning

confidence: 99%

Proinflammatory stimuli regulate endothelial hyaluronan expression and CD44/HA-dependent primary adhesion.

Mohamadzadeh¹,

DeGrendele²,

Arizpe³

et al. 1998

J. Clin. Invest.

287

240

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The localization of circulating leukocytes within inflamed tissues occurs as the result of interactions with and migration across vascular endothelium, and is governed, in part, by the expression of adhesion molecules on both cell types. Recently, we have described a novel primary adhesion interaction between the structurally activated form of the adhesion molecule CD44 on lymphocytes and its major ligand hyaluronan on endothelial cells under physiologic laminar flow conditions, and have proposed that this interaction functions in an extravasation pathway for lymphocytes in vascular beds at sites of inflammation. While the regulation of activated CD44 on leukocytes has been characterized in depth, regulation of hyaluronate (HA) on endothelial cells has not been extensively studied. Here we demonstrate that the expression of HA on cultured endothelial cell lines and primary endothelial cultures is inducible by the proinflammatory cytokines TNFalpha and IL-1beta, as well as bacterial lipopolysaccharide. In addition, this inducibility appears strikingly restricted to endothelial cells derived from microvascular, but not large vessel, sources. The elevated HA levels thus induced result in increased CD44-dependent adhesive interactions in both nonstatic shear and laminar flow adhesion assays. Changes in mRNA levels for the described HA synthetic and degradative enzymes were not found, suggesting other more complex mechanisms of regulation. Together, these data add to the selectin and immunoglobulin gene families a new inducible endothelial adhesive molecule, hyaluronan, and help to further our understanding of the potential physiologic roles of the CD44/HA interaction; i.e., local cytokine production within inflamed vascular beds may enhance surface hyaluronan expression on endothelial cells, thereby creating local sites receptive to the CD44/HA interaction and thus extravasation of inflammatory cells.

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“…Although CD44 is not necessary for the extravasation of lymphocytes into lymphoid organs, we demonstrate that CD44 plays a role in the generation of DTH responses. As with many other sites of increased cellular migration, such as the developing embryonic limb bud (38), inflammatory sites (33), and around metastatic tumor deposits (33), the deposition of HA within the DTH site is markedly enhanced (34,35). Given that CD44 binds HA, each of these sites is a potential area in which to look for CD44 receptor function.…”

Section: Discussionmentioning

confidence: 99%

CD44 is necessary for optimal contact allergic responses but is not required for normal leukocyte extravasation.

Camp

Scheynius

Johansson

et al. 1993

The Journal of Experimental Medicine

228

126

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SummaryThe in vivo administration of certain monoclonal antibodies (mAbs) against the adhesion receptor, CD44, into normal mice induces both a modulation of CD44 from the surface of peripheral lymphocytes, and a concomitant increase in the amount of soluble CD44 in the serum. CD44-negative lymphocytes isolated from anti-CD44-treated mice exhibit normal homing patterns upon adoptive transfer, and are capable of reexpressing CD44 upon activation. The treatment of haptensensitized mice with anti-CD44 mAb inhibits their ability to mount a cutaneous delayed-type hypersensitivity (DTH) response within the first 24 h after hapten challenge. This inhibition reflects a block in both the edema and leukocyte infiltration of the cutaneous site of DTH, whereas the extravasation and accumulation ofleukocytes in the draining lymph nodes progress normally. After 72 h, the leukocytes that extravasate into the site of antigen challenge express CD44. These results indicate that CD44 is not necessary for normal leukocyte circulation but is required for leukocyte extravasation into an inflammatory site involving nonlymphoid tissue.

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Increased hyaluronic acid is associated with dermal delayed-type hypersensitivity

Cited by 19 publications

References 10 publications

Circulating hyaluronate in psoriasis

Circulating hyaluronate in psoriasis

Proinflammatory stimuli regulate endothelial hyaluronan expression and CD44/HA-dependent primary adhesion.

CD44 is necessary for optimal contact allergic responses but is not required for normal leukocyte extravasation.

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