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Mechanism of the upregulation of erythropoietin-induced uptake clearance by the spleen.

Repeated administration of recombinant human erythropoietin (rhEPO) causes upregulation of receptor-mediated tissue uptake by the spleen (Kato, M., H. Kamiyama, A. Okazaki, K. Kumaki, Y. Kato, and Y. Sugiyama. J. Pharmacol. Exp. Ther. 283: 520-527, 1997). To discover whether such upregulation is due to an increase in target cells, the numbers of colony-forming unit erythroids (CFU-E) and burst-forming unit erythroids (BFU-E), the precursor of CFU-E, were measured in the spleen after rhEPO treatment. The uptake clearance of 125I-labeled rhEPO by the spleen was almost proportional to the number of CFU-E, suggesting that the upregulation is due to an increased number of CFU-E. When growth cells were metabolically labeled with [3H]thymidine in vivo, the radioactivity in bone marrow fell significantly after rhEPO treatment, whereas that in the spleen increased significantly. A cell-fractionation study using Percoll revealed that the radioactivity in the BFU-E fraction of splenic cells increased initially after rhEPO treatment, followed by an increase in radioactivity in the CFU-E fraction with a concomitant reduction in radioactivity in the BFU-E fraction. These results demonstrate that EPO stimulates the migration of BFU-E from bone marrow to spleen, followed by its differentiation into CFU-E in the spleen. In conclusion, the upregulation observed in the spleen is due to its stimulatory effect on the migration of BFU-E.

Animals↗

Carotid baroreceptor control of liver and spleen volume in cats.

We tested the hypothesis that the blood volumes of the spleen and liver of cats are reflexly controlled by the carotid sinus (CS) baroreceptors. In pentobarbital-anesthetized cats the CS area was isolated and perfused so that intracarotid pressure (Pcs) could be controlled while maintaining a normal brain blood perfusion. The volume changes of the liver and spleen were estimated by measuring their thickness using ultrasonic techniques. Cardiac output, systemic arterial blood pressure (Psa), central venous pressure, central blood volume, total peripheral resistance, and heart rate were also measured. In vagotomized cats, increasing Pcs by 100 mmHg caused a significant reduction in Psa (-67.8%), cardiac output (-26.6%), total peripheral resistance (-49.5%), and heart rate (-15%) and significantly increased spleen volume (9.7%, corresponding to a 2.1 +/- 0.5 mm increase in thickness). The liver volume decreased, but only by 1.6% (0.6 +/- 0.2 mm decrease in thickness), a change opposite that observed in the spleen. The changes in cardiovascular variables and in spleen volume suggest that the animals had functioning reflexes. These results indicate that in pentobarbital-anesthetized cats the carotid baroreceptors affect the volume of the spleen but not the liver and suggest that, although the spleen has an active role in the control of arterial blood pressure in the cat, the liver does not.

Animals↗

Spleen volume and blood flow response to repeated breath-hold apneas.

The purpose of this study was 1) to answer whether the reduction in spleen size in breath-hold apnea is an active contraction or a passive collapse secondary to reduced splenic arterial blood flow and 2) to monitor the spleen response to repeated breath-hold apneas. Ten trained apnea divers and 10 intact and 7 splenectomized untrained persons repeated five maximal apneas (A1-A5) with face immersion in cold water, with 2 min interposed between successive attempts. Ultrasonic monitoring of the spleen and noninvasive cardiopulmonary measurements were performed before, between apneas, and at times 0, 10, 20, 40, and 60 min after the last apnea. Blood flows in splenic artery and splenic vein were not significantly affected by breath-hold apnea. The duration of apneas peaked after A3 (143, 127, and 74 s in apnea divers, intact, and splenectomized persons, respectively). A rapid decrease in spleen volume ( approximately 20% in both apnea divers and intact persons) was mainly completed throughout the first apnea. The spleen did not recover in size between apneas and only partly recovered 60 min after A5. The well-known physiological responses to apnea diving, i.e., bradycardia and increased blood pressure, were observed in A1 and remained unchanged throughout the following apneas. These results show rapid, probably active contraction of the spleen in response to breath-hold apnea in humans. Rapid spleen contraction and its slow recovery may contribute to prolongation of successive, briefly repeated apnea attempts.

Adult↗

Strain differences in the expression of corticotropin-releasing hormone immunoreactivity in nerves that supply the spleen and thymus.

The existence of nerve fibers containing corticotropin-releasing hormone (CRH) immunoreactivity in primary and secondary lymphoid organs from three strains of young adult male rats was examined. Spleens and thymuses from Fischer 344 (F344), Sprague-Dawley (SD) and Lewis (LEW) rats were prepared for immunocytochemistry using antisera directed against CRH. In F344 and SD rats, we were unable to demonstrate CRH-immunoreactive nerves in either the thymus or the spleen. Despite the lack of CRH-containing nerves, CRH immunoreactivity was present in pleotropic cells in the septum, cortex and medulla of the thymus, and in the red and white pulp of spleens from F344 and SD rats. In contrast, CRH+ nerves were found in thymuses and spleens from LEW rats. CRH+ nerves coursed in the interlobular septa, capsule, cortex and medulla of the LEW rat thymus. Large CRH-immunoreactive nerve bundles were present in the hilar region of the LEW rat spleen, and individual CRH+ fibers coursed in the capsule, trabeculae, red pulp, venous sinuses and marginal zone of the white pulp of the spleen. These findings indicate strain differences in neurotransmitter-specific nerves that innervate the rat spleen and thymus under basal conditions.

Animals↗

The sympathetic control of blood supply is different in the spleen and lymph nodes.

OBJECTIVES: The noradrenergic innervation of lymphoid organs controls several immune cell functions and local blood perfusion. Considering that cell and antigen uptake depend on the blood supply to lymphoid organs, the hypothesis was tested that feedback signals from activated immune cells control sympathetic vasomotor activity. METHODS: We determined the blood flow in spleen and mesenteric lymph nodes (mLN) of Wistar Kyoto rats during immune stimulation with endotoxin (LPS; 10 microg/kg) and following disruption of the noradrenergic transmission. RESULTS: Our data indicate that (a) the splenic noradrenaline content, which reflects the density of the sympathetic innervation, is 5 times higher in the spleen than in other peripheral organs and the spleen receives stronger tonic sympathetic input than mLN; (b) immune stimulation with LPS causes a 4-fold increase in the IL-1beta production in the spleen, but only 2-fold in mLN; (c) IL-1beta causes an inhibition of the sympathetic vasoconstrictor tonus in the spleen, but has no significant effect on the noradrenergic vascular tonus in mLN, and (d) in mLN, the local hyperemia induced by LPS is attenuated by the degranulation of vesicular stores of histamine and serotonin, indicating that these monoamines participate in the vasodilator effect of LPS in mLN. CONCLUSIONS: The present experiments, taken together with our previous studies, indicate that the control of blood supply to the spleen and mLN involves different mechanisms. While blood perfusion in the spleen depends on the inhibition of the noradrenergic vasoconstriction by endogenously produced IL-1beta, other vasoactive mediators such as serotonin and histamine play a role in the control of mLN perfusion.

Animals↗

Splenectomy versus spleen-preserving surgery for splenic echinococcosis.

BACKGROUND/AIMS: The spleen is the third most common location of hydatid disease after liver and lung. The aim of this study was to analyse the long-term outcome of surgical treatment of patients with splenic echinococcosis comparing splenectomy with spleen-preserving surgery. METHODS: During a period of 25 years (1976-2001), 19 (5.4%) patients with splenic echinococcosis were treated in our department out of 349 patients with abdominal hydatid disease. In 16 patients the spleen was the only organ involved, while in 3 patients the liver was also affected. RESULTS: Eleven patients had splenectomy and in the other 8 the spleen was preserved: enucleation (n = 4), partial cystectomy and omentoplasty (n = 2) and cystojejunal Roux-en-Y anastomosis (n = 2). One (6%) patient died in the early postoperative period and 5 (29%) patients had postoperative complications. There was no significant difference between the splenectomy and spleen-preserving groups concerning median hospital stay and postoperative complication rate. The median follow-up in 15 patients was 52 (range 6-300) months. Two patients (13%) developed recurrence of the disease requiring re-operation at 2 and 3 years, respectively. Recurrence occurred in 1 (12%) patient in the splenectomy group and in 1 (14%) out of 7 patients in the spleen-preserving group. CONCLUSION: In the present series it was possible to preserve the spleen in 8 (42%) of 19 patients, without significant increase of recurrent echinococcosis.

Adult↗

Percutaneous application of peptidoglycan from Staphylococcus aureus induces mast cell development in mouse spleen.

BACKGROUND: Previously, we found that percutaneous application of peptidoglycan (PEG) from Staphylococcus aureus increased the number of mast cells in the dermis, as seen in patients with atopic dermatitis. However, the origin of the mast cells infiltrating the dermis was not known. Our aim was to determine the origin of the skin mast cells induced by the percutaneous PEG application in mice. METHODS: PEG was applied to barrier-disrupted abdominal skin of mice every 5 days. Twenty days after the first application, mast cells were detected in the spleen cells by alcian blue-safranin staining. Expression of mast cell proteases and cytokines in the skin or spleen was investigated by reverse transcription-polymerase chain reaction. RESULTS: Percutaneous application of PEG increased the numbers of alcian blue-positive and safranin-negative mast cells in the spleen. Reverse transcription-polymerase chain reaction analysis of the spleen showed that these mast cells expressed mouse mast cell protease (MMCP)-1, MMCP-4, MMCP-5, and mast cell carboxypeptidase, suggesting that they were immature cells positioned developmentally between mucosal mast cells and connective tissue mast cells. In vitro long-term culture of spleen cells in the presence of PEG induced mast cell development. The features of these mast cells were coincident with those seen in the spleens of PEG-applied mice. Furthermore, when mice were intradermally injected, their skin showed increased levels of expression of mRNAs of MMCP-4, MMCP-5, and mast cell carboxypeptidase, but not MMCP-1. Similar mRNA expression was observed in the skin of PEG-applied mice. CONCLUSIONS: Percutaneous application of PEG may lead to the development of mast cells in the spleens of mice and contribute to an increase in mast cell numbers in the dermis, as seen in the skin lesions of atopic dermatitis patients.

Administration, Cutaneous↗

Fibrinolytic and amidolytic activities of elastase-and chymotrypsin-like proteases in spleen and leukocytes of some mammals.

Nonplasmin-mediated fibrinolytic activities were extracted with 2 M NaCIO4 from the spleen and leukocytes of nine species of mammals. The amidolytic and fibrinolytic activities of extracts were measured using Suc-Ala-Tyr-Leu-Val-pNA for elastase-like protease (ELP) and Suc-Tyr-Leu-Phe-pNA (or Suc-Ile-Pro-Phe-pNA) for chymotrypsin-like protease (CLP). ELP and the fibrinolytic activity in the human spleen and leukocytes exhibited the highest values among the nine species. The relative order of amidolysis by CLP was as follows: hamster greater than rat greater than mouse greater than dog in the spleen and hamster greater than rat = ox greater than dog in leukocytes. Neither fibrinolytic nor amidolytic activity was measurable in spleens and leukocytes of pigs and rabbits. The ratios of ELP to CLP activity in the spleen or leukocytes of each of the species varied significantly from those observed in humans. The amidolytic activity of the spleen in control mice was low; however, that of mice which had been intraperitoneally inoculated with sarcoma 180 cells was enhanced and further accompanied by an increase in the number of granulocytes and in fibrinolytic activity. These results suggest that the enhancement of spleen amidolytic and fibrinolytic activities is induced by an increase of granulocytes in the circulation.

Animals↗

Corticotropin-releasing factor receptors in mouse spleen: identification, autoradiographic localization, and regulation by divalent cations and guanine nucleotides.

The radioligand [125I-Tyro]ovine CRF [( 125I] oCRF) was used to identify, characterize, and localize CRF receptors in a crude homogenate of mouse spleen. The binding was linear with increasing membrane protein concentration, saturable, and of high affinity. Scatchard analysis of [125I]oCRF saturation curves revealed a high affinity component with an apparent dissociation constant of 0.26 nM and a maximum receptor concentration of 8.74 fmol/mg protein. The relative affinities of various CRF-related and unrelated peptides at the [125I]oCRF-binding site in spleen correlate well with their reported potencies in eliciting ACTH release from the pituitary and their relative affinities for CRF receptors in brain. Consistent with a coupling of splenic CRF receptors to a guanine nucleotide regulatory protein, the binding of [125I]oCRF was increased by magnesium ions and decreased by guanine nucleotides in both mouse spleen and brain. Saturation analysis of [125I]oCRF binding at 0, 1, and 10 mM MgCl2, 10 mM MgCl2 plus 200 microM GTP, and 10 mM MgCl2 plus 50 microM 5'-guanylimidodiphosphate indicated that high affinity [125I]oCRF binding in both brain and spleen requires Mg2+; however, subtle differences were observed in the degree of sensitivity and mechanisms by which Mg2+ and guanine nucleotides regulated specific binding of [125I]oCRF to brain and spleen. Autoradiographic studies indicated that [125I]oCRF-binding sites were primarily localized to the red pulp and marginal zone regions of the spleen, which are known to contain high concentrations of macrophages. The absence of [125I]oCRF-binding sites in the periarteriolar and peripheral follicular white pulp regions suggests that neither T nor B lymphocytes have specific CRF-binding sites. In summary, we have identified a high affinity, magnesium-dependent, and guanine nucleotide-sensitive binding site for CRF in mouse spleen which appears to be localized primarily in splenic macrophages.

Animals↗

Ultrasound and Doppler features of accessory spleens and splenic grafts.

16 splenic grafts and 24 accessory spleens were evaluated with ultrasound, colour Doppler and power Doppler imaging, in order to compare the features of splenic grafts and accessory spleens. 12 splenic grafts (11 surgically implanted, 1 islet of splenosis) were detected in eight patients following splenectomy 6-12 months previously. Four of the surgically implanted splenic grafts were found in three patients following splenectomy 16-18 days previously. 21 accessory spleens were incidentally detected in 20 subjects who had not been operated upon, whereas three enlarged accessory spleens were found in 10 patients who underwent splenectomy 6-12 months previously. The size, shape, rim features, echogenicity, acoustic enhancement and vascularization of the splenic grafts and accessory spleens were evaluated. The splenic grafts were oval with lobulated margins, an inhomogeneous pattern in 36% and acoustic enhancement in 64%. Multiple feeding vessels arising from the surrounding tissue entered the periphery of 10 splenic grafts in the eight patients operated on 6-12 months previously, whereas no vascular signals were detected in the four splenic grafts of the three patients operated on 16-18 days ago. Accessory spleens were round with smooth echogenic margins and a vascular hilum arising from the splenic vessels. In conclusion colour Doppler and power Doppler allow differentiation between accessory spleens and splenic grafts basing on their shape and vascular supply.

Humans↗

Immediate-early, transient induction of the interleukin-1 beta gene in mouse spleen macrophages by ionizing radiation.

In murine spleen cells, x ray irradiation induces the expression of the IL-1 beta gene at multiple phases of the peak time. We analyzed the immediate-early phase of IL-1 beta mRNA accumulation. To determine the lineage of cells that showed the immediate response to irradiation, normal spleen cells were analyzed by Northern blotting and in situ hybridization after separation by magnetic antibodies against specific cell-surface antigens. Although most of the spleen macrophages continuously expressed a low level of IL-1 beta mRNA, a portion of the macrophage population transiently accumulated large amounts of IL-1 beta message immediately after irradiation. A macrophage-like leukemia cell line that resembles these inducible macrophages was identified. A similar immediate-early and transient increase in the IL-1 beta mRNA level occurred when cultured spleen cells were irradiated with a low dose (3 Gy) of x rays. In contrast, the x ray-inducible expression of the IL-1 beta gene was immediate and continuous, not transient, in spleen cells from whole-body irradiated mice. Results of the run-on transcription assay and the determination of the decrease in the message using cultured spleen and macrophage-like leukemia cells indicated that x ray irradiation appears to activate the transcription of the IL-1 beta gene and partially stabilize the message. The results show that the x ray-induced immediate-early accumulation of IL-1 beta mRNA is regulated at both the transcriptional and post-transcriptional levels in an as yet unidentified population of spleen macrophages.

Animals↗

Cadmium-induced liver, heart, and spleen lipid peroxidation in rats and protection by selenium.

The purpose of this study was to evaluate the effects of cadmium-induced peroxidative damage to rat liver, heart, and spleen. Sprague-Dawley rats were injected subcutaneously with a single dose of 25, 125, 500, or 1250 microg Cd/kg and evaluated 6, 12, 24, or 72 h later. Liver, heart, and spleen were analyzed for lipid peroxidation and Fe, Cu, Zn, Se, and Cd concentrations. Data showed that Cd produced enhanced lipid peroxidation in the liver, heart, and spleen. These Cd-induced changes were accompanied by a significant rise in liver, heart, and spleen Fe and Cu, and a fall in spleen Zn and liver, heart, and spleen Se. Concurrent treatment with Se and Cd reduced the Cd-induced alterations in liver, heart, and spleen peroxidation and essential metal levels. Data suggest that lipid peroxidation is associated with cadmium toxicity and that Se was found effective in preventing lipid peroxidation.

Animals↗

[Hyperbaric oxygen therapy in rats submitted to hepatic veins ligation: mortality valuation and histological study of liver and spleen].

PURPOSE: To evaluate the effects of hyperbaric oxygen therapy in rats submitted to instantaneously hepatic vein obstruction. METHODS: 30 Holtzman adult male rats were utilised, distributed into two groups: 1) hepatic vein obstruction; 2) hepatic vein obstruction associated with hyperbaric oxygen therapy. General anaesthesia was utilized by a solution composed of ketamine chloride (40 mg/ml) and meperidine chloride (10 mg/ml) in a dose of 50/mg/weight, applied into the right gluteus muscle. The animals belonged to group 2 were submitted to hyperbaric oxygen therapy, 8 hours after the operations, in a 2,5 atmosphere, which lasts 120 minutes per day, in consecutive 20 days. The statistical analysis was made in relation to mortality and histological study of livers and spleens utilizing the Fisher test, and the results were considered statistically significant when p < 0.05. RESULTS: Occurred seven (46.67%) deaths between animals belonged to group 1 and no deaths in the animals belonged to group 2. The histological studies made in the livers and spleens of the animals belonged to group 1 showed many alterations in the following percentages: thrombosis of hepatic, portal and center-lobular veins in five (33.3%), very extensive necrosis of liver cells in seven (46.7%), and light in eight (53.3%), Kupffer cells developed and hypertrophied in 14 (93.3%), high congestion of the spleen purple in six (40.0%) and moderate and severe hemossiderinosis spleen in 14 (93.3%). The analysis of this parameters in the group 2 only showed light necrosis of liver cells, Kupffer cells light developed and hypertrophied, moderated congestion of the spleen purple and light hemossiderinosis spleen. All these parameters analysed showed significantly difference (p < 0.05) between these two groups. CONCLUSIONS: It could be concluded that the hyperbaric oxygen therapy applied in rats, with instantaneously hepatic vein obstruction decreased their post-surgical mortality and their early deleterious effects in the liver and spleen.

Animals↗

[Partial resection of the spleen in the treatment of benign and traumatic lesions].

It has been thought that the spleen is an organ without important functions, until recently. That is, why splenectomy has been the procedure of choice in a treatment of splenic diseases. Even now, when we know the functional [figure: see text] importance of the spleen, splenectomy is performed frequently, regardless of its complications. The need of spleen functions salvage, favours partial resection of the spleen as competitive in a treatment of its traumatic and benign lesions. Improvement in diagnostic procedures, surgical techniques, transfusiology and postoperative treatment, will promote it as a treatment of choice. The authors of this study have experience with 17 partial resections of the spleen for traumatic, 11 for benign lesions of the spleen, and one ectopic spleen with hypersplenism, without mortality and with insignificant complications.

Humans↗

[Autotransplantation of the spleen].

Auto transplantation of the spleen can be performed in the patients with traumatic rupture of the spleen, in whom spleen could not be conserved in the other way. The right indication for this method is isolated rupture of the spleen (concvasation or complete devascularisation). This method is not recommended in the endangered patients, patients with previous disease of the spleen as well as in the patients with the perforation of the other abdominal organs at the same time. Auto transplantation was performed in 12 patients with isolated splenic rupture and hematoperitoneum, 11 men and one woman. The majority of patients are younger. In 8 patients, autotransplant was placed into big omentum, in three into lipomatous tissue surrounding left kidney, and in one into anterior abdominal wall. In all the patients from this group, following analysis were taken: MCV (middle volume of erythrocytes), HTC, Hb, Le, Glucose, urea, creatinin, sodium, potassium, alkali phosphatasis, target cells, Howell Jolly's bodies, Heinz's bodies, IgG, IgA, IgM, C3, C4, T3, T4, T8, B, segmentated, eosinophiles, lymphocytes, reticulocytes, thrombocytes, fibrinogen, PT, APTT, aggregation of thrombocytes and aggregation of thrombocytes on collagen. The same parameters were taken in 12 patients with surgery similar to splenectomy and in 12 after splenectomy. After splenectomy, there was decrease of the immunologic defending abilities of the organism because of the loss of the childrens function of the spleen, decreased level of the opsonines and tutsin, which leads to the impaired phagocytosis, decreased concentration of IgM and T and B lymphocytes, while in patients after auto transplantation the results were physiological. The most important thing in the assessment of the function of the autotransplanted spleen is scintigraphic investigation using 99mTc-denaturated red blood cells. In our study, auto transplant function was assessed in 10/12 patients by scintigraphy. Five years after surgery, no one patient was proved to have postsplenectomic sepsis.

Female↗

Host response to myeloma: effect of syngeneic spleen cells on the growth and function of MOPC 104E myeloma in vitro.

The effect of coculturing nonadherent and plastic adherent cells from the spleen with MOPC 104E KI81 for short (24 h) and long term (7 days) was investigated. In both culture systems, the effect of the spleen cells on the secretion of IgM by plaque-forming cells assay and growth of the plasmacytoma by cell counts and flow cytometry was measured. In these studies, a low effector:target (E:T) ratio which did not produce cytotoxicity to MOPC 104E cells was used. We observed that while nonadherent spleen cells from normal or MOPC 104E-primed mice inhibited secretion of IgM by the MOPC 104E cells, they stimulated the proliferation of MOPC 104E cells two times faster than MOPC 104E cells cultured alone. Plastic adherent cells from the spleens of normal mice or MOPC 104E-primed mice also inhibited secretion of IgM by the tumor cells as measured by plaque formation, and stimulated proliferation of MOPC 104E in 24 h coculture. Plastic adherent cells from normal nonprimed mice initially stimulated the myeloma to grow, but by 24 h, a large fraction of the population was in the G1 or possibly resting state. The effect of nonadherent and plastic adherent cells on the stem cell activity of MOPC 104E was also tested in 7-day colony-forming assays. Nonadherent cells had no effect on colony-forming units or plaque formation. Plastic adherent cells from normal spleen cells inhibited plaque formation by 68% but had no effect on colony formation. However, plastic adherent cells from spleens of mice primed in vivo with MOPC 104E tumor cells suppressed plaque formation by 98% and also reduced colony formation. The results showed that inhibition by macrophages of IgM production by MOPC 104E cells is independent of cell proliferation. The adherent macrophages from both normal and in vivo-primed spleen cells were Mac.1 positive after 7 days of coculture with MOPC 104E cells. However, the density of Mac.1 was greater on primed macrophages.

Animals↗

Comparative mitogenic responses of T-cells and B-cells in spleens of mice of varying age.

Mouse spleen cell mitogenic responses to Phytohemagglutinin (PHA), conconavalin A (con A), staphylococcal enterotoxin B (SEB) and lipopolysaccharide (LPS) were studied as a function of age. In CD-1 mice, spleen cell DNA synthesis in response to stimulation by PHA, con A and SEB varied from 18% - 33% of adult values for the first 3 weeks of life. By 6 weeks, the PHA response was 63% of the adult response and achieved adult values by 8 weeks of life. In contrast to these T-cell responses, DNA spleen cell synthesis in response to LPS was approximately that of adults as early as 7 days after birth. When spleen cell mitogenic responses were studied in C57B1/6J mice a similar pattern emerged. C57 spleen cell responses to PHA, con A and SEB varied from 24% - 54% of adult values for the first 3 weeks of life. By 4 weeks, spleen cell responses to PHA and con A were approximately those of adults. Again, C57 spleen cell responses to LPS were equivalent to adult values as early as 7 days after birth.

Absorption↗

Helper function of rat spleen cells reactive with guinea pig serum.

Treatment of rat spleen cells with normal guinea pig serum (GPS) has been shown to produce a significant loss of responsiveness to stimulation with either Con A or PHA. This phenomenon was seen even when the spleen cells were triggered with mitogens up to 96 hr after treatment with GPS, suggesting that GPS had produced a long-lasting alteration in some cells or removed a cell subpopulation. Glass-wool non-adherent spleen cells, known to produce greater responses that unfractionated spleen cells, also had their responses to Con A and PHA reduced by GPS treatment though the response was still greater than that of untreated, unfractionated cells, suggesting that the actual responder cells had been spared by GPS. Suppressor cells did not appear to be the target of GPS because such an effect would have resulted in increased responsiveness and the opposite result was obtained. That a helper cell was affected by GPS was suggested by the following observations: a) the virtually unresponsive GPS-treated spleen cells produced greater than normal responses after removal of glass-wool-adherent suppressor cells; b) the response of glass-wool-nonadherent spleen cells was significantly decreased after GPS treatment; and c) mixtures containing equal numbers of glass-wool-nonadherent and GPS-treated spleen cells also showed reduced responsiveness after GPS treatment.

Animals↗