REVIEW Sminia, T. (1989) Cell Tissue Res. 256, 431-438 32 Ivanoff, B., Andr4, C., Fontagnes, R. and Jourdan, G. 19 Hameleers, D.M.H., Van der Ven, I., Sminia, T. and (1982) Ann. Immunol. (Inst. Pasteur) 133D, 61-70 Biewenga, J. (1990) Res. Immunol. 141,515-528 33 Holt, P.G. and Sedgwick, J.D. (1987) Immunol. Today 8, 20 Hameleers, D.M.H., Van der Ven, I., Biewenga, J. and 14-15 Sminia, T. (1991) Immunol. Cell Biol. 69, 119-125 34 Sedgwick, J.D. and Holt, P.G. (1985) Cell. Immunol. 94, 21 Spit, B.J., Hendriksen, E.G.J., Bruijntjes, J.p. and Kuper, 182-194 C.F. (1989) Cell Tissue Res. 255, 193-198 35 Holt, P.G., Vines, J. and Britten, D. (1988) Immunology 22 Kuper, C.F., Spit, B.J., Bruijntjes, J.P., Hendriksen, E.G.J. 63,591-593 36 Kraal, G., Weissman, I.L. and Butcher, E.C. (1985) Adv. and Hameleers, D.M.H. (1989) in Nasal Carcinogenesis in Exp. Med. Biol. 186, 145-151 Rodents: Relevance to Human Health Risk (Feron, V.J. and Bosland, M.C., eds), pp. 30-36, Pudoc 37 Scicchitano, R., Husband, A.J. and Clancy, R.L. (1984) 23 Kuper, C.F., Hameleers, D.M.H., Bruijntjes, J.P. et al. Immunology 53,375-384 (1990) Cell Tissue Res. 259, 371-377 38 Sheldrake, R.F. (1989) Vet. Immunol. Immunopathol. 21, 24 Koornstra, P.J., De Jong, F.I.C.R.S., Vlek, L.F.M., 177-186 Marres, E.H.M.A. and Van Breda Vriesman, P.J.C. (1991) 39 Pals, S.T., Kraal, G., Horst, E. et al. (1986) J. Immunol. Acta Otolaryngol. 111,591-599 137, 760-763 25 Koornstra, P.J., Duijvestijn, A.M., De Jong, F.I.C.R.S. 40 Jeurissen, S.H.M., Claassen, E., Van Rooijen, N. and et al. (1991) in Lymphatic Tissues and in vivo Immune Kraal, G. (1985) Immunology 56, 417-423 Responses (Irnhof, B.A., Berrih-Aknin, S. and Ezine, S., eds), 41 Russell, M.W. and Mestecky, J. (1988) Rev. Infect. Dis. pp. 529-536, Marcel Dekker 10 (Suppl. 2), 440-446 26 Plesch, B.E.C. (1982) Adv. Exp. Med. Biol. 149, 491-497 42 Dijkstra, C.D., D6pp, E.A., Joling, P. and Kraal, G. 27 Butcher, E.C., Rouse, R.V., Coffman, R.L. et al. (1982) (1985) Immunology 54, 589-599 J. Immunol. 129, 2698-2707 43 Jeurissen, S.H.M. and Dijkstra, C.D. (1986) Eur. J. 28 Tilney, N.L. (1971) J. Anat. 109, 369-383 Immunol. 16, 562-568 29 Richardson, J., Bouchard, T. and Ferguson, C.C. (1976) 44 Sminia, T., Janse, E.M. and Plesch, B.E.C. (1983) Anat. Lab. Invest. 35,307-312 Rec. 207, 309-316 30 Tamura, S., Samegai, Y. and Kurata, T. (1988) Microbiol. 45 Sminia, T., Van der Brugge-Gamelkoorn, G.J. and Immunol. 32, 1145-1161 Jeurissen, S.H.M. (1989) Crit. Rev. Immunol. 9, 119-150 31 Lycke, N., Karlsson, U., Sjolander, A. and Magnusson, 46 Sminia, T. and Plesch, B.E.C. (1982) Virchows Arch. K.E. (1991) Scand. ]. Immunol. 33,691-698 (Cell. Pathol.) 40, 181-189

Regulatory mechanisms in leukocyte adhesion: flexible receptors for sophisticated travelers Ruggero Pardi, Luca Inverardi and Jeffrey R. Bender Unstimulated leukocytes spend extended periods circulating in the blood, punctuated by migration through lymphoid areas and peripheral tissues. During transit, strong cell-cell interactions control immune surveillance and specialized effector functions. The structures and mechanisms that allow this flexible adhesion and migration behavior are the subject of this review. Leukocyte adhesiveness is a finely regulated process, controlled by membrane receptors involved in cell-cell and cell-matrix recognition (Table 1). Leukocyte adhesion receptors fluctuate between low-and high-avidity states for their respective ligands, depending on triggering events delivered by the surrounding cells and the extracellular milieu. Among the controlling factors are antigen-presenting and antigen-bearing cells, vascular

addressins and various kinds of matrixproteins, exposed during normal leukocyte trafficking or as a consequence of pathological events. In addition to the intrinsic properties of adhesion receptors and ligands, such as surface density and diffusivity, both positive and negative feedback loops affect leukocyte adhesion and trafficking, through a network of intracellular signalling pathways.

© 1992, ElsevierSciencePublishers Ltd, UK.

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REVIEW Microenvironmental influences on leukocyte adhesiveness

Table 1. Families of adhesion molecules and their counter-receptors

Antigen-dependent adhesion

For lymphocytes expressing fully competent surface antigen receptors, the recognition of antigen in a cellbound form has long been recognized as a very efficient and selective stimulus capable of triggering increased cell-cell junctional avidity 1. Cells whose 'stickiness' can be regulated by antigen recognition include mature T and B cells2,3, in addition to leukocytes that express Fcy receptors armed with antigen-reactive immunoglobulins, such as natural killer (NK) cells and neutrophils4. When cell-bound antigen is recognized, lymphocytes undergo dramatic morphological changes, implying cytoskeletal rearrangement, which ultimately lead to increased area of contact, adhesion strengthening and reorientation of the lymphocyte protein secretory apparatus towards the bound target celP. Until recently, it was thought that weak intercellular adhesion, mediated by structures such as lymphocyte function-associated antigen-1 (LFA-1) and CD2 on the surface of the lymphocyte, preceded antigen-specific interaction, achieving thermodynamically more favorable conditionss. This sequence of events has not been formally ruled out, as weak cell-cell interactions cannot be easily analysed in vitro; however, recent findings