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The Journal of Immunology, 1973, 111: 33-37.
Copyright © 1973 by The American Association of Immunologists, Inc.

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Lysosomal Enzyme Release from Human Leukocytes: Mediation by the Alternate Pathway of Complement Activation1

Ira M. Goldstein2, Melchiorre Brai3, Abraham G. Osler4 and Gerald Weissmann5

From the Department of Medicine, New York University School of Medicine, New York, New York 10016, and the Department of Medical Immunology, The Public Health Research Institute of the City of New York, New York

Abstract

The alternate pathway of complement activation has recently assumed an important role in the mediation of inflammation and tissue injury. We have found that complement activated via this pathway interacts with human polymorphonuclear leukocytes (PMN) in the absence of particulates and stimulates the selective release of lysosomal enzymes. Fresh human serum, after treatment with zymosan or cobra venom factor, yields a fluid phase component which induces cytochalasin B-treated PMN to release beta-glucuronidase without leakage of cytoplasmic lactate dehydrogenase. Involvement of the alternate pathway of complement activation is evidenced by failure of serum to yield enzyme-releasing activity after pretreatment with rabbit antihuman C3 proactivator, 0.01 M EDTA but not 0.01 M EDTA, 0.02 M salicylaldoxime, 0.02 M hydrazine or by heating to 56°C for 30 min. Levels of C3 proactivator in treated sera correlated inversely with and perturbs the PMN plasma membrane sufficiently to cause lysosomal membrane perturbation, fusion, and ultimately lysosomal enzyme extrusion by a process of "reverse endocytosis."

Footnotes

1 This work was supported by grants from The National Institutes of Health (AM-11949; AI-08710), the New York Heart Association, the Whitehall Foundation, American Cancer Society, Inc. (IC-391) and the National Science Foundation (GB-31738X).

2 Instructor, Department of Medicine, New York University School of Medicine, New York, N. Y. Recipient of NIH Special Fellowship (1 F03 CA 55226-01) from the National Cancer Institute.

3 Department of Medical Immunology, The Public Health Research Institute of the City of New York, New York, N. Y.

4 Department of Medical Immunology, The Public Health Research Institute of the City of New York, New York, N. Y.

5 Professor, Department of Medicine, New York University School of Medicine, New York, N. Y.




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