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In monocytes, sulfatide, a lipid from Mycobacterium tuberculosis, blocked priming for enhanced release of superoxide (02-) by the macrophage activating factors lipopolysaccharide, gamma interferon, interleukin-l1 (IL-1,), tumor necrosis factor alpha (TNF-a), and muramyl dipeptide. Sulfatide, in the presence of lipopolysaccharide, also caused increased secretion of IL-1I and TNF-oa into monocyte culture medium. Sulfatide altered the pattern of phosphorylation of monocyte proteins. Cell lysates prepared from monocytes treated with sulfatide showed decreased activity of protein kinase C, but sulfatide did not directly inhibit protein kinase C activity when added to lysates. A known inhibitor of protein kinase C, staurosporine, also inhibited 02 release and caused increased secretion of IL-1,B. Thus, sulfatide appeared to indirectly affect protein kinase C, implicating protein kinase C as part of the mechanism of priming. Because sulfatide blocked priming for enhanced release of 02which could interfere with monocyte bactericidal activity, while causing enhanced secretion of IL-1, and TNF-a, which could promote formation of granulomata, sulfatide might be an important factor in the pathogenesis of M. tuberculosis.

A B S T R A C T During phagocytosis, neutrophils release a variety of substances that include activators and inactivators ofchemotactic factors. It is generally considered that these represent hydrolytic enzymes. Elastase and cathepsin G, major proteases released from lysosomal granules during phagocytosis, contain broad hydrolytic activity. This study examined granule elastase and cathepsin G for their role as inactivators of chemotactic factors. Elastase and cathepsin G were purified from human neutrophils by Trasylol-Sepharose and CM-cellulose chromatography. Small amounts (-3 ,g, 1 ,M) of elastase and cathepsin G, comparable to quantities released by 106 neutrophils during phagocytosis, completely inactivated the C5 chemotactic factor generated in human serum. Larger concentrations were needed to inactivate the C3 chemotactic factor, and when the bacterial chemotactic factor from Escherichia coli was employed, five times more elastase or cathepsin G was ineffective against this chemotactic factor. Supernatant fluid from human neutrophils that had ingested complement-coated zymosan particles contained elastase and cathepsin G and had inactivator activity for both the C5 chemotactic fragment and the bacterial factor. A specific inhibitor of elastase largely abolished the inactivator activity in the phagocytic supernates that was directed against C5 factor but did not affect the inactivator activity for the bacterial factor. Similar results occurred in studies of granule lysates. These data indicate heterogeneity in the chemotactic factor inactivator activity released by phagocytosing neutrophils. The INTRODUCTIONDuring phagocytosis, polymorphonuclear leukocytes (neutrophils) release factors that both activate and inactivate neutrophil chemotactic factors. The activation occurs primarily through effects on the alternate complement pathway, resulting in generation of chemotactic fragments from C5, and these chemotactic fragments can also be generated as well as inactivated by direct interaction with a C5-cleaving enzyme released during phagocytosis (1,2).Two types of substances inhibitory for neutrophil chemotaxis are released from phagocytizing leukocytes. These include a cell-directed inhibitor, termed the neutrophil-immobilizing factor, which directly blocks cellular responses to chemotactic factors, and a second factor which appears to inactivate the C5 chemotactic fragment (1,3). Published data indicate that the neutrophil-immobilizing factor is heat stable, whereas the inactivator activity of the C5 chemotactic fragment is heat labile at 56°C (1, 3).The present study describes further the heat labile chemotactic factor inhibitor activity released by phagocytizing leukocytes. This inhibitory activity affects not only the C5 chemotactic fragment, but also the C3 chemotactic fragment and the bacterial chemotactic

A 63-year-old man was initially seen with multiple pulmonary nodules 14 years after a left parotidectomy for an epithelial-myoepithelial carcinoma of salivary gland. Eight and 18 months after parotidectomy, the patient had local recurrence of his salivary gland tumor. He remained disease-free before being seen with pulmonary nodules, which were evaluated by open lung biopsy. The pathologic features of the pulmonary nodules were identical to the salivary gland tumor resected 14 years earlier. This is the fourth reported case of epithelial-myoepithelial carcinoma of salivary gland metastasizing to a distant site.

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