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

van Spriel, AB Leusen, JHW van Egmond, M Dijkman, HBPM Assmann, KJM Mayadas, TN van de Winkel, JGJ

Ab. Van Spriel et al., Mac-1 (CD11b/CD18) is essential for Fc receptor-mediated neutrophil cytotoxicity and immunologic synapse formation, BLOOD, 97(8), 2001, pp. 2478-2486

73

INGLESE

Article

Hematology,"Cardiovascular & Hematology Research

BLOOD

0006-4971 → ACNP

97

8

2001

2478 - 2486

ISI

0006-4971(20010415)97:8<2478:M(IEFF>2.0.ZU;2-O

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 PM Ns, Mac-1-deficient mouse PMNs, and mouse PMNs transgenic for human FcR. Al l PMNs efficiently phagocytosed Ab-coated particles, However, antibody-depe ndent cellular cytotoxicity (ADCC) was abrogated in Mac-1(-/-) PMNs and in human PMNs blocked with anti-Mac-1 monoclonal Ab (mAb). Mac-1(-/-) PMNs wer e unable to spread on Ab-opsonized target cells and other Ab-coated surface s. Confocal laser scanning and electron microscopy revealed a striking diff erence in immunologic synapse formation between Mac1(-/-) and wild-type PMN s. Also, respiratory burst activity could be measured outside membrane-encl osed 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, impaire d formation of immunologic synapses, and absent tumor cytolysis. (Blood, 20 01;97: 2478-2486) (C) 2001 by The American Society of Hematology.