Function of the urokinase receptor (CD87) in neutrophil chemotaxis.
During recruitment, leukocytes respond to chemotaxins and traverse matrix barriers. Urokinase-type plasminogen activator (uPA), bound to its receptor (uPAR; CD87) facilitates plasmin formation, which promotes matrix proteolysis. Polymorphonuclear leukocytes (PMNs) are critical to the inflammatory response and express both uPA and CD87. To determine whether uPA and CD87 are required for PMN chemotaxis, PMNs were pretreated with an anti-CD87 monoclonal antibody (mAb), a neutralizing anti-uPA mAb, or uPA. PMN chemotaxis was profoundly suppressed by the anti-CD87 mAb but was unaffected by anti-uPA mAb or uPA. The role CD87 plays in chemotaxis may be related to its ability to associate with CR3. CD87/CR3 coupling can be disrupted by specific saccharides. The same saccharides that disrupt CD87/CR3 coupling (NADG, D-mannose, and mannoside) inhibit PMN chemotaxis. We conclude that CD87 plays a crucial role in PMN chemotaxis in vitro that is independent of uPA enzyme activity but may be related to the ability of CD87 to interact with CR3.
Gyetko
M R
MR
Division of Pulmonary and Critical Care Medicine, Ann Arbor Veterans Affairs Medical Center, Michigan 48103-0360, USA.
Sitrin
R G
RG
Fuller
J A
JA
Todd
R F
RF
Petty
H
H
Standiford
T J
TJ
D000911:Antibodies, Monoclonal; D002478:Cells, Cultured; D002630:Chemotactic Factors / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D006801:Humans; D016209:Interleukin-8 / Q000494:pharmacology; D016177:Macrophage-1 Antigen / Q000502:physiology; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000502:physiology*; D009844:Oligosaccharides / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000502:physiology*; D055293:Receptors, Urokinase Plasminogen Activator; D015398:Signal Transduction
D000911:Antibodies, Monoclonal; D002630:Chemotactic Factors; D016209:Interleukin-8; D016177:Macrophage-1 Antigen; D009844:Oligosaccharides; C524898:PLAUR protein, human; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D009240:N-Formylmethionine Leucyl-Phenylalanine