A novel biologic function of serum amyloid A. Induction of T lymphocyte migration and adhesion.
In the course of an inflammatory response, the concentration of serum amyloid A (SAA), a hepatocyte-derived acute phase protein, increases up to 1000-fold above the normal level. Although SAA was previously thought to be immunosuppressive, we recently reported that SAA is a potent chemoattractant for monocytes and neutrophils. The present study shows that recombinant human (rh) SAA also induces directional migration of T cells in vitro. Phenotypic analyses revealed that CD4+ and CD8+ T cell subsets were equally responsive to rhSAA, whereas CD45RA cells were also not selectively attracted by rhSAA. The T cell chemotaxis induced by rhSAA was inhibited by pretreatment of cells with pertussis toxin, suggesting the interaction of rhSAA with a G-protein-coupled receptor species. T cells pretreated with an optimal concentration of SAA exhibited enhanced adherence to human umbilical cord endothelial cell monolayers. Subcutaneous administration of rhSAA into huPBL-SCID mice caused the infiltration of human T lymphocytes at the injection sites by 4 h. These results suggest that SAA may play an important role in recruiting T lymphocytes, as well as neutrophils and monocytes into inflammatory lesions.
Xu
L
L
Biological Carcinogenesis and Development Program, Program Resources Inc./DynCorp, Frederick Cancer Research and Development Center, MD 21702, USA.
Badolato
R
R
Murphy
W J
WJ
Longo
D L
DL
Anver
M
M
Hale
S
S
Oppenheim
J J
JJ
Wang
J M
JM
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D004730:Endothelium, Vascular / Q000166:cytology; D006801:Humans; D016130:Immunophenotyping; D051379:Mice; D016513:Mice, SCID; D011994:Recombinant Proteins / Q000494:pharmacology; D000685:Serum Amyloid A Protein / Q000494:pharmacology / Q000502:physiology*; D013047:Specific Pathogen-Free Organisms; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000502:physiology* / Q000637:transplantation; D014471:Umbilical Veins
D011994:Recombinant Proteins; D000685:Serum Amyloid A Protein