Trafficking of CD44-deficient murine lymphocytes under normal and inflammatory conditions.
CD44 has been implicated in hyaluronan (HA)-dependent primary adhesion between leukocytes and endothelium. We studied the trafficking of lymphocytes of CD44-deficient DBA/1 mice under normal conditions, and during chronic and transient forms of inflammation. Animals homozygous for the CD44 mutation (CD44(-/-)) showed no abnormalities in the composition of the lympho-hemopoietic system, but their leukocytes could not recognize HA as an adhesion ligand. T cells from CD44-deficient mice responded normally to immunization with type II collagen or stimulation with a bacterial superantigen. Lymphocytes harvested from naive CD44(-/-) and wild-type (WT) animals showed similar trafficking properties when injected into naive recipients. However, cells from WT and CD44-deficient mice with collagen-induced arthritis showed distinct migration kinetics upon transfer to arthritic recipients. While lymphocytes from CD44(-/-) mice preferentially homed to lymph nodes, their entry into the inflamed synovial joints was delayed as compared with WT cells. Similar differences were observed in the migration kinetics of CD44-deficient and CD44-competent (CD44(+/+)) lymphocytes in bacterial superantigen-induced peritonitis. These results suggest that CD44 plays opposite roles in the regulation of leukocyte traffic to inflammatory sites versus the lymph nodes. CD44-deficient lymphocytes from animals with chronic arthritis, but not from those with transient peritonitis, expressed markedly reduced levels of the lymph node homing receptor, L-selectin. Extreme down-modulation of L-selectin from CD44(-/-) cells in arthritic condition might be a counter-regulatory response, which, by extending lymphocyte transit time in the circulation at the expense of lymph node homing, allows CD44-deficient cells to gain entry to the site of chronic inflammation via secondary adhesion mechanisms.
Section of Biochemistry and Molecular Biology, Department of Orthopedic Surgery, Rush University at Rush-Presbyterian-St. Luke's Medical Center, Chicago 60612, USA.
Reinout
R
Stoop
István
I
Gál
Tibor T
TT
Glant
John D
JD
McNeish
Katalin
K
Mikecz
D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology*; D002448:Cell Adhesion; D002634:Chemotaxis, Leukocyte / Q000502:physiology*; D002908:Chronic Disease; D024043:Collagen Type II / Q000276:immunology; D004768:Enterotoxins / Q000276:immunology / Q000633:toxicity; D018960:Hyaluronan Receptors / Q000502:physiology*; D006820:Hyaluronic Acid / Q000502:physiology; D019041:L-Selectin / Q000502:physiology; D017710:Lymphocyte Transfusion; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D010538:Peritonitis / Q000139:chemically induced / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D016201:Receptors, Lymphocyte Homing / Q000276:immunology; D018089:Superantigens / Q000276:immunology / Q000633:toxicity
D024043:Collagen Type II; D004768:Enterotoxins; D018960:Hyaluronan Receptors; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016201:Receptors, Lymphocyte Homing; D018089:Superantigens; D019041:L-Selectin; C031818:enterotoxin B, staphylococcal; D006820:Hyaluronic Acid