Mechanism of cytotoxicity of human large granular lymphocytes: relationship of the cytotoxic lymphocyte protein to the ninth component (C9) of human complement.

Abstract:

:A Mr 70,000 protein was isolated from cytotoxic human large granular lymphocytes and shown to have cytotoxic activity. The protein was demonstrated to be immunochemically related to the ninth component (C9) of complement and was therefore designated C9-related protein (C9RP). This finding suggests that C9RP and C9 share homology in primary structure and have a common evolutionary ancestry. C9RP was isolated, by affinity chromatography employing anti-human C9-Sepharose, from either purified cytoplasmic granules or whole-cell lysates of cultured human large granular lymphocytes. The cells were isolated from healthy blood donors and maintained in interleukin-2-dependent cultures. The immunochemical crossreactivity of C9 with C9RP was 3-4%, using a murine anti-C9RP antiserum. Certain murine monoclonal antibodies to C9RP and to C9 inhibited killing of K562 cells by human large granular lymphocytes. Killed target cells, identified by propidium iodide staining and isolated by fluorescence-activated cell-sorting, exhibited clusters of circular membrane lesions that resembled poly(C9) in appearance. Polymerization of isolated C9RP in the presence of Ca2+ resulted in the formation of two different circular structures, one having an inner diameter of approximately equal to 60 A, and the other, of 125 A. Polymerized C9RP could be incorporated into liposomes and, as such, gave rise to channels of two different sizes. The smaller channel had a functional diameter of 50-90 A, and the bigger channel, a diameter greater than 102 A.

authors

Zalman LS,Brothers MA,Chiu FJ,Müller-Eberhard HJ

doi

10.1073/pnas.83.14.5262

subject

Has Abstract

pub_date

1986-07-01 00:00:00

pages

5262-6

issue

14

eissn

0027-8424

issn

1091-6490

journal_volume

83

pub_type

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