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Vaccination as an adjuvant to chemotherapy of klebsiella pneumonia infection in mice
261
PRESENCE OF A LECTIN-LIKE RECEPTOR FOR BORDETELLA PERTUSSIS ENDOTOXIN ON RABBIT PERITONEAL MACROPHAGES, R,CHABY, N,HAEFFNER-CAVAILLON & L,SZABO, I n s t i t u t Sciences de Paris-Sud, 91405 0rsay - France.
44
de Biochimie, Facult~ des
A tritium labeled LPS (3H-LPS) was used to examine the binding characteristics of B.pertussis endotoxin to resident or elicited rabbit macrophages. The binding of the l a b e l e d to peritoneal macrophages was shown to be time-dependent, dose-dependent, saturable, reversible and specific, whereas no specific binding could be observed on lung macrophages. The specific binding was completely inhibited by the homologous unlabeled LPS but not at all by LPS obtained from Proteus mirabilis, establishing ligand specificity of the binding site. A 100% inhibition of the 3H-LPS binding was obtained with the polysaccharide PS-1 derived from the B.pertussis endotoxin but this binding was neither inhibited by the two other fractions PS-2 and Lipid-A of the same endotoxin, nor by many other neutral or anionic polysaccharides. Furthemore, an anti-PSol serum was also able to inhibit e f f i c i e n t l y the 3H-LPS binding. These data strongly suggest that recognition of B.pertussis LPS by rabbit peritoneal macrophages is mediated by a lectin-like receptor. EFFECT OF i.p. (.PARVUM ON THE TUMORICIDAL ACTIVITY OF TUMOR-ASSOCIATED TUMOR-ASSOCIATED LYMPHOCYTES FROM ASCITIC OVARIAN TUMORS.
MACROPIIAGES AND
45
M. Introna °, C. Seasa °°, G. Peri °, P. Allavena °, N. Polentarutti °, C. Mangioni °° and A. Mantovani°; °Istituto di Ricerche Farmacologiche "Mario Negri", Milan; °° Obstetric and Gynecologic Department, S. Gerardo Hospital, University of Milan, Milan, Italy Eight patients with epithelial ascitic ovarian tumors resistant to conventional chemotherapy were given i . p . C . p a r v u m (14 mg on day 0 and 7; 7 mg on day 30 and then at monthly intervals). In 2 patients ascitic fluid wag reduced after C. parvum and in other 3 complete disappearance of carcinomatous ascites was observed. 3 patients were completely unrespohsive to therapy. Solid tumor ma:;ses were not affected. Cytological esamination of ascitic fluid samples revealed a decrease in tumor cell numbers and an increase in macrophage and polymorph numbers. After treat~,ent with C.parvum, tumor-associated macrophages (TAM) were obtained in increased numbers but they showed no consistent increase in their spontaneous tumoricidal capacity nor increased responsiveness to lymphokines or interferon, l&-21 days after the first C.parvum inoculation, a marked decrease of the cytolytic capacity of TAM was observed, cytotoxicity returning to pretreatment values thereafter. Tumor-associated lymphoid cells, isolated by separation on discontinuous gradients showed no increase in ~ activity or numbers. Thus C.parvum reduces ovarian carcinomatous ascites through mechanism which remain to be fully defined. VACCINATION
AS AN ADJUVANT TO CHEMOTHERAPY
Mary L. S. Queiroz, Department
Mawer,
of Pharmacology
Oxford Road, Vaccination
Manchester,
response
effect on survival.
and in proportion However,
as an adjuvant to treatment
when cor~pared
Protection
University
of Manchester,
to the reduction
when vaccination of chemotherapy
with gentamicin,
in the im~.Lune response
was complete when
the mice.
of the interval
Protection between
decreased
infection
was made twelve hours after the there was no significant
effect on the
as measured by the number of survival,
with infected mice treated with gentamicin
Some parameters
IN MICE
of s fatal dose of K. pneumonia
was carried out five days before infecting
and vaccination.
INFECTION
N.
of Bacteriology,
in mlce 2,3, or 5 days before injection
szgniflcantly
infect!on
Bathirunathan,
and Department
PNEUMONIA
MI3 9PT, U.K.
in mice have a significant vaccination
G.E.,
OF KLEBSIELLA
alone.
on the above results are analysed.
46
PRESENCE OF A LECTIN-LIKE RECEPTOR FOR BORDETELLA PERTUSSIS ENDOTOXIN ON RABBIT PERITONEAL MACROPHAGES, R,CHABY, N,HAEFFNER-CAVAILLON & L,SZABO, I n s t i t u t Sciences de Paris-Sud, 91405 0rsay - France.
44
de Biochimie, Facult~ des
A tritium labeled LPS (3H-LPS) was used to examine the binding characteristics of B.pertussis endotoxin to resident or elicited rabbit macrophages. The binding of the l a b e l e d to peritoneal macrophages was shown to be time-dependent, dose-dependent, saturable, reversible and specific, whereas no specific binding could be observed on lung macrophages. The specific binding was completely inhibited by the homologous unlabeled LPS but not at all by LPS obtained from Proteus mirabilis, establishing ligand specificity of the binding site. A 100% inhibition of the 3H-LPS binding was obtained with the polysaccharide PS-1 derived from the B.pertussis endotoxin but this binding was neither inhibited by the two other fractions PS-2 and Lipid-A of the same endotoxin, nor by many other neutral or anionic polysaccharides. Furthemore, an anti-PSol serum was also able to inhibit e f f i c i e n t l y the 3H-LPS binding. These data strongly suggest that recognition of B.pertussis LPS by rabbit peritoneal macrophages is mediated by a lectin-like receptor. EFFECT OF i.p. (.PARVUM ON THE TUMORICIDAL ACTIVITY OF TUMOR-ASSOCIATED TUMOR-ASSOCIATED LYMPHOCYTES FROM ASCITIC OVARIAN TUMORS.
MACROPIIAGES AND
45
M. Introna °, C. Seasa °°, G. Peri °, P. Allavena °, N. Polentarutti °, C. Mangioni °° and A. Mantovani°; °Istituto di Ricerche Farmacologiche "Mario Negri", Milan; °° Obstetric and Gynecologic Department, S. Gerardo Hospital, University of Milan, Milan, Italy Eight patients with epithelial ascitic ovarian tumors resistant to conventional chemotherapy were given i . p . C . p a r v u m (14 mg on day 0 and 7; 7 mg on day 30 and then at monthly intervals). In 2 patients ascitic fluid wag reduced after C. parvum and in other 3 complete disappearance of carcinomatous ascites was observed. 3 patients were completely unrespohsive to therapy. Solid tumor ma:;ses were not affected. Cytological esamination of ascitic fluid samples revealed a decrease in tumor cell numbers and an increase in macrophage and polymorph numbers. After treat~,ent with C.parvum, tumor-associated macrophages (TAM) were obtained in increased numbers but they showed no consistent increase in their spontaneous tumoricidal capacity nor increased responsiveness to lymphokines or interferon, l&-21 days after the first C.parvum inoculation, a marked decrease of the cytolytic capacity of TAM was observed, cytotoxicity returning to pretreatment values thereafter. Tumor-associated lymphoid cells, isolated by separation on discontinuous gradients showed no increase in ~ activity or numbers. Thus C.parvum reduces ovarian carcinomatous ascites through mechanism which remain to be fully defined. VACCINATION
AS AN ADJUVANT TO CHEMOTHERAPY
Mary L. S. Queiroz, Department
Mawer,
of Pharmacology
Oxford Road, Vaccination
Manchester,
response
effect on survival.
and in proportion However,
as an adjuvant to treatment
when cor~pared
Protection
University
of Manchester,
to the reduction
when vaccination of chemotherapy
with gentamicin,
in the im~.Lune response
was complete when
the mice.
of the interval
Protection between
decreased
infection
was made twelve hours after the there was no significant
effect on the
as measured by the number of survival,
with infected mice treated with gentamicin
Some parameters
IN MICE
of s fatal dose of K. pneumonia
was carried out five days before infecting
and vaccination.
INFECTION
N.
of Bacteriology,
in mlce 2,3, or 5 days before injection
szgniflcantly
infect!on
Bathirunathan,
and Department
PNEUMONIA
MI3 9PT, U.K.
in mice have a significant vaccination
G.E.,
OF KLEBSIELLA
alone.
on the above results are analysed.
46