Leukocyte trafficking in a mouse model for leukocyte adhesion deficiency II/congenital disorder of glycosylation IIc.

Abstract:

: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.

journal_name

Blood

journal_title

Blood

authors

Yakubenia S,Frommhold D,Schölch D,Hellbusch CC,Körner C,Petri B,Jones C,Ipe U,Bixel MG,Krempien R,Sperandio M,Wild MK

doi

10.1182/blood-2008-01-132035

subject

Has Abstract

pub_date

2008-08-15 00:00:00

pages

1472-81

issue

4

eissn

0006-4971

issn

1528-0020

pii

blood-2008-01-132035

journal_volume

112

pub_type

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