| Autor: |
van Spriel, Annemiek B., Leusen, Jeanette H. W., van Egmond, Marjolein, Dijkman, Henry B. P. M., Assmann, Karel J. M., Mayadas, Tanya N., van de Winkel, Jan G. J. |
| Zdroj: |
Blood; April 2001, Vol. 97 Issue: 8 p2478-2486, 9p |
| Abstrakt: |
Receptors for human immunoglobulin (Ig)G and IgA initiate potent cytolysis of antibody (Ab)-coated targets by polymorphonuclear leukocytes (PMNs). Mac-1 (complement receptor type 3, CD11b/CD18) has previously been implicated in receptor cooperation with Fc receptors (FcRs). The role of Mac-1 in FcR-mediated lysis of tumor cells was characterized by studying normal human PMNs, Mac-1–deficient mouse PMNs, and mouse PMNs transgenic for human FcR. All PMNs efficiently phagocytosed Ab-coated particles. However, antibody-dependent cellular cytotoxicity (ADCC) was abrogated in Mac-1−/− PMNs and in human PMNs blocked with anti–Mac-1 monoclonal Ab (mAb). Mac-1−/− PMNs were unable to spread on Ab-opsonized target cells and other Ab-coated surfaces. Confocal laser scanning and electron microscopy revealed a striking difference in immunologic synapse formation between Mac-1−/− and wild-type PMNs. Also, respiratory burst activity could be measured outside membrane-enclosed compartments by using Mac-1−/− PMNs bound to Ab-coated tumor cells, in contrast to wild-type PMNs. In summary, these data document an absolute requirement of Mac-1 for FcR-mediated PMN cytotoxicity toward tumor targets. Mac-1−/− PMNs exhibit defective spreading on Ab-coated targets, impaired formation of immunologic synapses, and absent tumor cytolysis. |
| Databáze: |
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