Journal Article

The role of α<sub>4</sub> and LFA-1 integrins in selectin-independent monocyte and neutrophil migration to joints of rats with adjuvant arthritis

Ulrieke Birner, Thomas B. Issekutz, Ulrike Walter and Andrew C. Issekutz

in International Immunology

Published on behalf of Japanese Society for Immunology

Volume 12, issue 2, pages 141-150
Published in print February 2000 | ISSN: 0953-8178
Published online February 2000 | e-ISSN: 1460-2377 | DOI: http://dx.doi.org/10.1093/intimm/12.2.141
The role of α4 and LFA-1 integrins in selectin-independent monocyte and neutrophil migration to joints of rats with adjuvant arthritis

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Monocytes and neutrophils are chronically recruited to joints in rheumatoid arthritis. In the joints of rats with adjuvant arthritis, this is mediated, in part, by selectin-dependent and selectin-independent mechanisms. To define the selectin-independent mechanisms, 51Cr-labeled blood monocytes, 111In-labeled neutrophils and function blocking mAb to the selectins and integrins were utilized. Integrins contributed to the selectin-independent monocyte migration to arthritic joints with 58–70% inhibition of this recruitment by anti-α4 or anti-LFA-1 mAb, relative to selectin blockade alone. α4 plus P-selectin blockade was as effective as combined blockade of α4, P-, E- and L-selectin, mediating ~83% of the overall monocyte migration to the joints. In contrast, LFA-1 was the predominant selectin-independent mechanism for neutrophil recruitment to the joints. LFA-1 together with P-selectin had essential roles in the talar joint. In dermal inflammation in the arthritic rats, LFA-1 accounted for most (69%) of the selectin-independent monocyte migration to the chemoattractant C5adesArg (zymosan-activated serum), whereas LFA-1 and Mac-1 both contributed to selectin-independent neutrophil recruitment to C5adesArg. α4 integrin and P-selectin in concert mediated monocyte recruitment to lipopolysaccharide and IFN-γ lesions (81%). Thus: (1) either α4 or LFA-1 can mediate monocyte migration to arthritic joints in the absence of selectin function and α4 together with P-selectin is particularly important; (2) LFA-1 is the predominant mechanism of selectin-independent migration of neutrophils to inflamed joints; and (3) in arthritic rats, selectin-independent migration of monocytes and neutrophils to dermal inflammation is mediated by α4 or LFA-1 or both LFA-1 and Mac-1, depending on the leukocyte type, and inflammatory stimulus.

Keywords: adhesion molecule; CD11a; CD49d; inflammation; leukocyte; ACD acid–citrate–dextrose; CAM cell adhesion molecule; LPS lipopolysaccharide; PPP platelet-poor plasma; ZAS zymosan-activated serum

Journal Article.  7337 words.  Illustrated.

Subjects: Immunology ; Biological Sciences

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