Leukocyte trafficking in a mouse model for leukocyte adhesion deficiency II/congenital disorder of glycosylation IIc.
Leukocyte adhesion deficiency II (LAD II), also known as congenital disorder of glycosylation IIc (CDG-IIc), is a human disease in which a defective GDP-fucose transporter (SLC35C1) causes developmental defects and an immunodeficiency that is based on the lack of fucosylated selectin ligands. Since the study of in vivo leukocyte trafficking in patients with LAD II is experimentally limited, we analyzed this process in mice deficient for Slc35c1. We found that E-, L-, and P-selectin-dependent leukocyte rolling in cremaster muscle venules was virtually absent. This was accompanied by a strong but not complete decrease in firm leukocyte adhesion. Moreover, neutrophil migration to the inflamed peritoneum was strongly reduced by 89%. Previous reports showed surprisingly normal lymphocyte functions in LAD II, which indicated sufficient lymphocyte trafficking to secondary lymphoid organs. We now found that while lymphocyte homing to lymph nodes was reduced to 1% to 2% in Slc35c1(-/-) mice, trafficking to the spleen was completely normal. In accordance with this, we found a defect in the humoral response to a T cell-dependent antigen in lymph nodes but not in the spleen. Taken together, Slc35c1(-/-) mice show strongly defective leukocyte trafficking but normal lymphocyte homing to the spleen, which may explain normal lymphocyte functions in LAD II.
Max Planck Institute for Molecular Biomedicine, Münster, Germany.
Sviatlana
S
Yakubenia
David
D
Frommhold
Dirk
D
Schölch
Christina C
CC
Hellbusch
Christian
C
Körner
Björn
B
Petri
Claire
C
Jones
Ute
U
Ipe
M Gabriele
MG
Bixel
Robert
R
Krempien
Markus
M
Sperandio
Martin K
MK
Wild
D000818:Animals; D002448:Cell Adhesion; D002634:Chemotaxis, Leukocyte; D004195:Disease Models, Animal; D036904:Leukocyte Rolling; D018370:Leukocyte-Adhesion Deficiency Syndrome / Q000276:immunology*; D008198:Lymph Nodes / Q000473:pathology; D026901:Membrane Transport Proteins / Q000172:deficiency*; D051379:Mice; D009004:Monosaccharide Transport Proteins; D018482:Muscle, Skeletal / Q000098:blood supply; D009504:Neutrophils / Q000473:pathology; D009928:Organ Specificity; D013154:Spleen; D014699:Venules / Q000166:cytology
D026901:Membrane Transport Proteins; D009004:Monosaccharide Transport Proteins; C520021:Slc35c1 protein, mouse