Rat blood neutrophils express very late antigen 4 and it mediates migration to arthritic joint and dermal inflammation

doi:10.1084/jem.183.5.2175

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Rat blood neutrophils express very late antigen 4 and it mediates migration to arthritic joint and dermal inflammation

TB Issekutz, M Miyasaka and AC Issekutz
Department of Medicine, University of Toronto, Ontario, Canada.

Blood neutrophils contribute to joint injury in human and experimental models of arthritis. Neutrophil migration out of the blood in joint inflammation involves both the CD18 (beta2) integrins and a CD18 integrin-independent pathway. To investigate this migration, radiolabeled rat blood neutrophils were used to measure neutrophil accumulation in the inflamed joints of rats with adjuvant arthritis and the role of leukocyte integrins in migration to these joints and to dermal inflammation was determined. Neutrophils migrated rapidly (<2 h) to the inflamed joints 14-18 d after immunization with adjuvant. Blocking monoclonal antibodies (mAbs) to both LFA-1 and Mac-1 together, as well as a mAb to CD18, inhibited neutrophil accumulation in the inflamed joints by 50-75%. However, migration to dermal inflammation induced by C5a(des Arg)' tumor necrosis factor alpha, lipopolysaccharide, and poly-inosine:cytosine was inhibited by approximately 90%. Flow cytometry revealed the expression of low levels of very late antigen 4 (VLA-4) on nearly all rat blood neutrophils. Treatment with anti-VLA-4 plus anti-LFA-1 but neither mAb alone, strongly (60-75%) inhibited neutrophil accumulation in arthritic joints. This mAb combination also inhibited neutrophil migration to dermal inflammatory reactions by 30-70%. Blocking VLA-4 together with the CD18 integrins inhibited neutrophil accumulation by 95-99%, virtually abolishing neutrophil accumulation in cutaneous inflammation. A similar blockade of VLA-4 and CD18 decreased neutrophil accumulation in the inflamed joints by 70-83%, but a significant portion of the neutrophil accumulation to these joints still remained. In conclusion, rat blood neutrophils express functional VLA-4 that can mediate neutrophil migration to both inflamed joints and dermal inflammatory sites. VLA-4 appears to be able to substitute for LFA-1 in this migration and is particularly important for accumulation in inflamed joints. However, there exists an additional CD18- and VLA-4-independent pathway of neutrophil migration to arthritic joints that is not involved in acute dermal inflammation.
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Reinhardt, P. H., Kubes, P. (1998). Differential Leukocyte Recruitment From Whole Blood Via Endothelial Adhesion Molecules Under Shear Conditions. Blood 92: 4691-4699 [Abstract] [Full Text]
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Werr, J., Xie, X., Hedqvist, P., Ruoslahti, E., Lindbom, L. (1998). beta 1 Integrins Are Critically Involved in Neutrophil Locomotion in Extravascular Tissue In Vivo. J. Exp. Med. 187: 2091-2096 [Abstract] [Full Text]
Newham, P., Craig, S. E., Clark, K., Mould, A. P., Humphries, M. J. (1998). Analysis of Ligand-Induced and Ligand-Attenuated Epitopes on the Leukocyte Integrin {alpha}4{beta}1: VCAM-1, Mucosal Addressin Cell Adhesion Molecule-1, and Fibronectin Induce Distinct Conformational Changes. J. Immunol. 160: 4508-4517 [Abstract] [Full Text]
Davenpeck, K. L., Sterbinsky, S. A., Bochner, B. S. (1998). Rat Neutrophils Express alpha 4 and beta 1 Integrins and Bind to Vascular Cell Adhesion Molecule-1 (VCAM-1) and Mucosal Addressin Cell Adhesion Molecule-1 (MAdCAM-1). Blood 91: 2341-2346 [Abstract] [Full Text]
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Mizgerd, J. P., Kubo, H., Kutkoski, G. J., Bhagwan, S. D., Scharffetter-Kochanek, K., Beaudet, A. L., Doerschuk, C. M. (1997). Neutrophil Emigration in the Skin, Lungs, and Peritoneum: Different Requirements for CD11/CD18 Revealed by CD18-deficient Mice. J. Exp. Med. 186: 1357-1364 [Abstract] [Full Text]
Reinhardt, P. H., Ward, C. A., Giles, W. R., Kubes, P. (1997). Emigrated Rat Neutrophils Adhere to Cardiac Myocytes via {alpha}4 Integrin. Circ. Res. 81: 196-201 [Abstract] [Full Text]
Reinhardt, P. H., Elliott, J. F., Kubes, P. (1997). Neutrophils Can Adhere Via alpha 4beta 1 -Integrin Under Flow Conditions. Blood 89: 3837-3846 [Abstract] [Full Text]