Cell surface expression of the 300 kDa mannose-6-phosphate receptor by activated T lymphocytes.
Phosphosugars, such as mannose-6-phosphate (M6P), have been shown previously to display anti-inflammatory properties, notably inhibition of experimental autoimmune encephalomyelitis (EAE) and adjuvant-induced arthritis in rats. It has been proposed that M6P exerts its anti-inflammatory effect by displacing lysosomal enzymes, which are involved in T-cell extravasation into inflammatory sites, from the 300 kDa mannose-6- phosphate receptor (MPR-300) on the surface of T cells. If this model is correct MPR-300 should be selectively expressed on the surface of activated T cells, as T cell entry into the central nervous system in EAE depends on the T cells being in an activated state. Thus, the present study examines whether cell surface expression of MPR-300 by T lymphocytes correlates with their state of activation and whether T cells in inflammatory sites express the receptor. Flow cytometric studies showed MPR-300 to be absent from the surface of unstimulated rat T cells isolated from peripheral blood and lymphoid tissues, and T cells resident within the peritoneal cavity. In contrast, MPR-300 was expressed on activated T cells derived from an inflammatory peritoneal exudate. In vitro studies demonstrated transient expression of MPR-300 on the surface of splenic T cells following stimulation with Con A. MPR-300 was also induced on T-cell lines by antigen stimulation. These data demonstrate that T cells in inflammatory sites express MPR-300 on their surface and activation of T lymphocytes induces cell surface expression of MPR-300. Such findings are consistent with the hypothesis that cell surface MPR-300 is required for the entry of T cells into inflammatory sites.
Hindmarsh
E J
EJ
Division of Immunology and Cell Biology, John Curtin School of Medical Research, Australian National University, Canberra, Australian Capital Territory, Australia.
Staykova
M A
MA
Willenborg
D O
DO
Parish
C R
CR
D000818:Animals; D001202:Ascitic Fluid / Q000737:chemistry / Q000166:cytology; D003208:Concanavalin A / Q000494:pharmacology; D005260:Female; D005434:Flow Cytometry; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D017527:Receptor, IGF Type 2 / Q000737:chemistry / Q000378:metabolism*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D013864:Thioglycolates / Q000494:pharmacology
D017527:Receptor, IGF Type 2; D013864:Thioglycolates; D003208:Concanavalin A