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Hemopoietic effects of intravenous soluble glucan
3[}5
IIN~OPOIETIC EFFE6"TS OF IffrRA~NOU$ SOLU~I.~ GLUttoN
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M.L. Patchen and T.J. MacVittie The Armed Forces Radiobiology Research Institute, Bethesda, MD, USA A soluble form of the reticuloendothelial- and immune-modulating agent gluten (gluten-F) has been evaluated for its ability to modulate hemopoiesis. A single 5.0 mg intravenous injection of glucan-F into C3H/HeN mice increased peripheral white blood cellularity, bone marrow and splenic cellularity, bone marrow and splenic granulocyte-macrophage progenitor cell (GM-CFC) numbers, and splenic pluripotent stem cell (CFU-s) and erythroid progenitor cell (CFU-e) numbers. Serum levels of granulocyte-macrophage colony stimulating activity (CSA) were also extremely elevated following glucan-F administration. These hemopoietic responses correlate well with those previously shown to be produced by intravenous particulate gluten (glucan-P) administration. In contrast to glucan-P, however, intravenous glucan-F administration does not induce granuloma formation and severe hepatosplenomegaly, thus making glucan-F's clinical application more feasible than that of glucan-P.
M E D I A T O R S AND M E C H A N I S M S 1 MODIFICATION OF THE EXPRESSION OF THE CSb RECEPTOR BY 15-HETE
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J. Cook, S. Delebass4e, J.C. Aldigier, N. Gualde and M. Kazatc~klne Groupe de Recherche au~Immunologie et Biochimie, U.E.R. de M4decine, Limoges and Laboratoire du Compl4ment, I.N.S.E.R.M. U28, H~pital Broussais, Paris, France. We have studied the effect of the lipoxygenase metabolite, 15-HETE on the expression of the human C3b receptor (CRI) by a B lymphocyte enriched population of human peripheral blood leukocytes. B lymphocytes were isolated from donors whose HLA group was known and the baseline number of CR1 sites was determined by an eqmlbrium binding study using an 125i labeled mouse monoclonal antibody directed ag%flnst the receptor. After overnight culture in completed RMPI alone or containing I0-6M, I0-7M or 10~ M final concentration of 15-HETE, the number of receptor sites/B lymphocyte was again quantitated. It appears that 15-HETE treatment modifies the expression of CRI on B cells. This phenomenon may be linked %o the HLA phenotype. E A R L Y R E V E R S I B L E STEPS D U R I N G P H A INDUCED H U M A N L Y M P H O C Y T E S ACTIVATION: C H A N G E S IN C H R O M A T I N O R G A N I Z A T I O N , A C T I N P O L Y M E R I Z A T I O N AND C A L M O D U L I N LEVEL. A.POMPIDOU-P.MICHEL-D.ESNOUS-H.VAINER Facul't~ de M ~ d e c i n e Cochin PARIS F RAN~----~E Early events during PHA induced lymphocyte activation occur within 1 hour reported here are results on:a)the structural changes in hetero-euchromatin,as measured by the nuclear refringency method.b)the G-F actin transition states evaluated by the DNase I inhibition test-both performed by using intact cells and c)the intracellular C a M level as measured in an acellular extract by the radioimmunoassay(NEN).ln all cases,results are expressed as percentages from control values(determined in corresponding non activated cells. At i0 m n following cell stimulation,actin polymerization reached a maximum(~0%DNasel inhibition)which does not be totaly restored by HCL Guanidine treatment-like the chromatin dispersion,it is blocked by the cells preincubation with the competitive sugar(N-Acetylgalactosamin).At 20 ran,maximal chromatin dispersion(10%)in intact cells and 40-50% decrease of the immunoreactive calmodulin level in the acellular extract were observed.After 60 ran,all these parameters come back t~control values. Thus,although it is not yet possible to formulate established interrelationships between the reversible changes observed. These data emphasize a role for these major cellular compounds on the early step occuring during the PHA induced activation of h u m a n lymphocytes.
29
IIN~OPOIETIC EFFE6"TS OF IffrRA~NOU$ SOLU~I.~ GLUttoN
25
M.L. Patchen and T.J. MacVittie The Armed Forces Radiobiology Research Institute, Bethesda, MD, USA A soluble form of the reticuloendothelial- and immune-modulating agent gluten (gluten-F) has been evaluated for its ability to modulate hemopoiesis. A single 5.0 mg intravenous injection of glucan-F into C3H/HeN mice increased peripheral white blood cellularity, bone marrow and splenic cellularity, bone marrow and splenic granulocyte-macrophage progenitor cell (GM-CFC) numbers, and splenic pluripotent stem cell (CFU-s) and erythroid progenitor cell (CFU-e) numbers. Serum levels of granulocyte-macrophage colony stimulating activity (CSA) were also extremely elevated following glucan-F administration. These hemopoietic responses correlate well with those previously shown to be produced by intravenous particulate gluten (glucan-P) administration. In contrast to glucan-P, however, intravenous glucan-F administration does not induce granuloma formation and severe hepatosplenomegaly, thus making glucan-F's clinical application more feasible than that of glucan-P.
M E D I A T O R S AND M E C H A N I S M S 1 MODIFICATION OF THE EXPRESSION OF THE CSb RECEPTOR BY 15-HETE
28
J. Cook, S. Delebass4e, J.C. Aldigier, N. Gualde and M. Kazatc~klne Groupe de Recherche au~Immunologie et Biochimie, U.E.R. de M4decine, Limoges and Laboratoire du Compl4ment, I.N.S.E.R.M. U28, H~pital Broussais, Paris, France. We have studied the effect of the lipoxygenase metabolite, 15-HETE on the expression of the human C3b receptor (CRI) by a B lymphocyte enriched population of human peripheral blood leukocytes. B lymphocytes were isolated from donors whose HLA group was known and the baseline number of CR1 sites was determined by an eqmlbrium binding study using an 125i labeled mouse monoclonal antibody directed ag%flnst the receptor. After overnight culture in completed RMPI alone or containing I0-6M, I0-7M or 10~ M final concentration of 15-HETE, the number of receptor sites/B lymphocyte was again quantitated. It appears that 15-HETE treatment modifies the expression of CRI on B cells. This phenomenon may be linked %o the HLA phenotype. E A R L Y R E V E R S I B L E STEPS D U R I N G P H A INDUCED H U M A N L Y M P H O C Y T E S ACTIVATION: C H A N G E S IN C H R O M A T I N O R G A N I Z A T I O N , A C T I N P O L Y M E R I Z A T I O N AND C A L M O D U L I N LEVEL. A.POMPIDOU-P.MICHEL-D.ESNOUS-H.VAINER Facul't~ de M ~ d e c i n e Cochin PARIS F RAN~----~E Early events during PHA induced lymphocyte activation occur within 1 hour reported here are results on:a)the structural changes in hetero-euchromatin,as measured by the nuclear refringency method.b)the G-F actin transition states evaluated by the DNase I inhibition test-both performed by using intact cells and c)the intracellular C a M level as measured in an acellular extract by the radioimmunoassay(NEN).ln all cases,results are expressed as percentages from control values(determined in corresponding non activated cells. At i0 m n following cell stimulation,actin polymerization reached a maximum(~0%DNasel inhibition)which does not be totaly restored by HCL Guanidine treatment-like the chromatin dispersion,it is blocked by the cells preincubation with the competitive sugar(N-Acetylgalactosamin).At 20 ran,maximal chromatin dispersion(10%)in intact cells and 40-50% decrease of the immunoreactive calmodulin level in the acellular extract were observed.After 60 ran,all these parameters come back t~control values. Thus,although it is not yet possible to formulate established interrelationships between the reversible changes observed. These data emphasize a role for these major cellular compounds on the early step occuring during the PHA induced activation of h u m a n lymphocytes.
29