International Immunology, Vol. 12, No. 2, 141-150,
February 2000
© 2000 Japanese Society for Immunology
The role of 
4 and LFA-1 integrins in selectin-independent monocyte and neutrophil migration to joints of rats with adjuvant arthritis
1 Departments of 1Pathology,
2 Pediatrics and
3 Microbiology–Immunology, Dalhousie University, Halifax, Nova Scotia B3J 3G9, Canada
Correspondence to: A. C. Issekutz, Department of Pediatrics, Division of Immunology, Rheumatology and Infectious Diseases, IWK Grace Health Centre, 5850 University Avenue, Halifax, Nova Scotia B3J 3G9, Canada
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-
4 or anti-LFA-1 mAb, relative to selectin blockade alone. 4 plus P-selectin blockade was as effective as combined blockade of 4, 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. 4 integrin and P-selectin in concert mediated monocyte recruitment to lipopolysaccharide and IFN-
lesions (81%). Thus: (1) either 4 or LFA-1 can mediate monocyte migration to arthritic joints in the absence of selectin function and 4 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 4 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
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