Expression of L-selectin, but not CD44, is required for early neutrophil extravasation in antigen-induced arthritis.
L (leukocyte)-selectin (CD62L) and CD44 are major adhesion receptors that support the rolling of leukocytes on endothelium, the first step of leukocyte entry into inflamed tissue. The specific contribution of L-selectin or CD44 to the regulation of cell traffic to joints in arthritis has not been investigated. We used CD44-deficient, L-selectin-deficient, and CD44/L-selectin double knockout mice to determine the requirement for these receptors for inflammatory cell recruitment during Ag-induced arthritis. Intraperitoneal immunization resulted in similar activation status and Ag-specific responses in wild-type and gene-targeted mice. However, extravasation of neutrophil granulocytes, but not the emigration of T cells, into the knee joints after intra-articular Ag injection was significantly delayed in L-selectin-deficient and double knockout mice. Intravital videomicroscopy on the synovial microcirculation revealed enhanced leukocyte rolling and diminished adherence in mice lacking either CD44 or L-selectin, but CD44 deficiency had no significant effect on the recruitment of L-selectin-null cells. Compared with wild-type leukocytes, expression of L-selectin was down-regulated in CD44-deficient cells in the spleen, peripheral blood, and inflamed joints, suggesting that reduced expression of L-selectin, rather than the lack of CD44, could be responsible for the delayed influx of granulocytes into the joints of CD44-deficient mice. In conclusion, there is a greater requirement for L-selectin than for CD44 for neutrophil extravasation during the early phase of Ag-induced arthritis.
Szántó
Sándor
S
Section of Biochemistry and Molecular Biology, Department of Orthopedic Surgery, Rush University Medical Center, Chicago, IL 60612, USA.
Gál
István
I
Gonda
Andrea
A
Glant
Tibor T
TT
Mikecz
Katalin
K
D000818:Animals; D001168:Arthritis / Q000276:immunology* / Q000473:pathology; D002450:Cell Communication; D002465:Cell Movement; D042783:Endothelial Cells / Q000502:physiology; D018960:Hyaluronan Receptors / Q000032:analysis / Q000502:physiology*; D019041:L-Selectin / Q000032:analysis / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009504:Neutrophils / Q000502:physiology*; D012710:Serum Albumin, Bovine / Q000276:immunology
D018960:Hyaluronan Receptors; D019041:L-Selectin; D012710:Serum Albumin, Bovine