The Leukocyte Integrins

Abstract

polymorphonuclear leukocyte intercellular adhesion molecule metal ion-dependent adhesion site phosphatidylinositol protein kinase C pleckstrin homology focal adhesion kinase leukocyte adhesion deficiency type I Leukocytes are marrow-derived cells of diverse form and function that circulate in the blood in a quiescent state of low adhesiveness before migrating into tissues to defend against invading microbes, participate in immune functions and wound repair, or become fixed extracellular residents. Some, such as T-lymphocytes, recirculate and traverse blood, organ, and lymphatic compartments during long cycles of immune surveillance. Others, notably polymorphonuclear leukocytes (PMNs,1 neutrophils), are rapid response cells specialized for acute spatially targeted defensive actions that can be mounted in minutes. Leukocytes are also effectors of pathologic inflammation when their accumulation and actions are disregulated. Integrins on their surfaces, together with other plasma membrane adhesion molecules, are required for interactions of leukocytes with endothelial cells and other cell types and with matrix structures (1Kishimoto T.K. Baldwin E.T. Anderson D.C. Gallin J.I. Snyderman R. Inflammation: Basic Principles and Clinical Correlates. 3rd Ed. Lippincott Williams and Wilkins, Philadelphia1999: 537-570Google Scholar). 2The β2 integrins are comprehensively reviewed in Ref. 1Kishimoto T.K. Baldwin E.T. Anderson D.C. Gallin J.I. Snyderman R. Inflammation: Basic Principles and Clinical Correlates. 3rd Ed. Lippincott Williams and Wilkins, Philadelphia1999: 537-570Google Scholar. In the last decade dozens of reviews and hundreds of primary reports on leukocyte function, leukocyte integrins, and specific aspects of the biology of integrins have appeared. We used many that could not be cited because of space limitations and will provide a list of these on request. The functional state, density, and topography of integrins on leukocytes are regulated by lipid, cytokine, and chemokine signaling molecules and by “cross-talk” from other surface adhesion molecules (1Kishimoto T.K. Baldwin E.T. Anderson D.C. Gallin J.I. Snyderman R. Inflammation: Basic Principles and Clinical Correlates. 3rd Ed. Lippincott Williams and Wilkins, Philadelphia1999: 537-570Google Scholar, 2Lorant D.E. Patel K.D. McIntyre T.M. McEver R.P. Prescott S.M. Zimmerman G.A. J. Cell Biol. 1991; 115: 223-234Crossref PubMed Scopus (545) Google Scholar, 3Rainger G.E. Buckley C. Simmons D.L. Nash G.B. Curr. Biol. 1997; 7: 316-325Abstract Full Text Full Text PDF PubMed Scopus (83) Google Scholar, 4Feldhaus M.J. Kessel J.M. Zimmerman G.A. McIntyre T.M. J. Immunol. 1998; 161: 6280-6287PubMed Google Scholar, 5Campbell J.J. Hendrick K. Zlotnick A. Siani M.A. Thompson D.A. Butcher E.C. Science. 1998; 279: 381-384Crossref PubMed Scopus (844) Google Scholar, 6Johnston B. Burns A.R. Suematsu M. Issekutz T.B. Woodman R.C. Kubes P. J. Clin. Invest. 1999; 103: 1269-1276Crossref PubMed Scopus (170) Google Scholar). Each class of leukocytes displays a particular pattern of integrins that can change in a signal- and time-dependent fashion. For example, resting human T lymphocytes (T cells) express β1, β2, and β7 integrins, but this varies with the subclass and is altered by immune stimulation (5Campbell J.J. Hendrick K. Zlotnick A. Siani M.A. Thompson D.A. Butcher E.C. Science. 1998; 279: 381-384Crossref PubMed Scopus (844) Google Scholar). Freshly isolated human monocytes express β1 and β2 integrins, but their culture and/or differentiation into macrophages changes the pattern and induces αvβ3 (5Campbell J.J. Hendrick K. Zlotnick A. Siani M.A. Thompson D.A. Butcher E.C. Science. 1998; 279: 381-384Crossref PubMed Scopus (844) Google Scholar, 7Krissansen G.W. Elliott M.J. Lucas C.M. Stomski F.C. Berndt M.C. Cheresh D.A. Lopez A.F. Burns G.F. J. Biol. Chem. 1990; 265: 823-830Abstract Full Text PDF PubMed Google Scholar). Human PMNs, once thought to express only β2 integrins, display β1 and β3 heterodimers and use them in motility and migration (8Bohnsack J.F. Akiyama S.K. Damsky C.H. Knape W.A. Zimmerman G.A. J. Exp. Med. 1990; 171: 1221-1237Crossref PubMed Scopus (113) Google Scholar, 9Kubes P. Niu X.F. Smith C.W. Kehrli Jr., M.E. Reinhardt P.H. Woodman R.C. FASEB J. 1995; 9: 1103-1111Crossref PubMed Scopus (169) Google Scholar, 10Hendey B. Lawson M. Marcantonio E.E. Maxfield F.R. Blood. 1996; 87: 2038-2048Crossref PubMed Google Scholar, 11Yauch R.L. Berditchevski F. Harler M.B. Reichner J. Hemler M.E. Mol. Biol. Cell. 1998; 9: 2751-2765Crossref PubMed Scopus (271) Google Scholar, 12Taooka Y. Chen J. Yednock T. Sheppard D. J. Cell Biol. 1999; 145: 413-420Crossref PubMed Scopus (241) Google Scholar). A common feature, however, is that each leukocyte subtype expresses one or more members of the β2 integrin family. Further, the β2 heterodimers are restricted to cells of the leukocyte lineage. The remainder of this minireview will focus on the structure and function of t