Mac-1 (CD11b/CD18) is essential for Fc receptor–mediated neutrophil cytotoxicity and immunologic synapse formation

AB van Spriel, JHW Leusen… - Blood, The Journal …, 2001 - ashpublications.org
AB van Spriel, JHW Leusen, M van Egmond, HBPM Dijkman, KJM Assmann, TN Mayadas…
Blood, The Journal of the American Society of Hematology, 2001ashpublications.org
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 …
Abstract
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.
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