Premium
CD11/CD18‐independent transendothelial migration of human polymorphonuclear leukocytes and monocytes: involvement of distinct and unique mechanisms
Author(s) -
Issekutz Andrew C.,
Chuluyan H. Eduardo,
Lopes Nancy
Publication year - 1995
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.57.4.553
Subject(s) - cd18 , monocyte , biology , integrin , chemotaxis , umbilical vein , microbiology and biotechnology , lymphocyte function associated antigen 1 , endothelium , tumor necrosis factor alpha , cell adhesion molecule , immunology , in vitro , intercellular adhesion molecule 1 , receptor , biochemistry , endocrinology
Monocytes and polymorphonuclear leukocytes (PMNLs) migrate across cytokine (interleukin‐1, tumor necrosis factor) activated endothelium or unstimulatcd endothelium in response to chemotactic factors in vitro and in vivo utilizing the CD11/CD18 (i.e., β 2 integrin) adhesion molecule complex. However, in vivo studies have suggested that under some conditions and/or in certain tissues, leukocyte migration can also proceed via CD11/CD18‐independent mechanisms. Here we com pared adhesion mechanisms involved in the migration of 51 Cr‐Iabeled blood monocytcs and PMNLs across human umbilical vein endothelium (HUVE) monolayers. We ob served that monocyte transendothelial migration was not inhibited by monoclonal antibody (mAb) to CD18, when the HUVE was activated with IL‐1 and the chemotactic factor C5a induced the migration. This CD18‐independent monocyte migration was blocked by treatment of the monocyte with mAb to β 1 , or α 4 integrin, suggesting that very late activation antigen 4 (VLA‐4) on the monocyte served as the alternative migration mechanism. In con trast to monocytes, mAb to CD18 inhibited PMNL migration to C5a across IL‐l‐aetivated HUVE, but only by 66%, significantly less than with C5a alone (84%) or IL‐l‐aetivated HUVE alone (95%). The migration of anti‐CD18 mAb‐treated PMNLs was not inhibited by function‐blocking mAbs to sialyl Lewis*, L'Selectin, β 1 or of 4 integrin, the β 3 ‐related leukocyte response integrin, IL‐8, or platelet‐activating factor (PAF) antagonists, alone or in combination. Antibody‐blocking studies of the ligands on HUVE indicated that E‐selectin may be partially involved in this CD18‐independent PMNL migration but that ICAM‐1, VCAM‐1, PECAM‐1, and P‐sclectin are not involved. Of several chemotactic factors tested, C5a and C5a desArg in activated plasma were the most active in inducing CD18‐independent migration of PMNLs across IL‐l‐aetivated HUVE. These results demonstrate that (1) monocytes can utilize VLA‐4 for op timal transendothelial migration and (2) PMNLs may have a novel CDl8‐independent migration mechanism that is activated by C5a in conjunction with one or more ligands on cytokine‐activated endothelium. This may in volve, in part, E‐selectin interacting with a yet to be identified counterreceptor on PMNLs. J . Lcukoc. Biol. 57: 553–561; 1995.